bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypokalemic paralysis; an unusual presentation of Conn's Syndrome
Authors: Güller Pınar Üzgeç , Şahin Alak Zehra Yağmur , Güçlü Metin , Kıyıcı Sinem
Published: January 2023

Introduction

Primary aldosteronism (PA) is the most common cause of secondary hypertension. It is caused by excessive aldosterone secretion in adrenal cortex. The typical presentation of PA at young patients, is resistant hypertension and hypokalemia. In recently published series, potassium levels are frequently reported normal. Normotension is also rare in these patients. We report a case of PA, presenting with hypokalemic paralysis and normal blood pressure, atypically.

Clinical Case

A 33-year-old female patient with fatigue, muscle weakness and difficulty walking, was admitted to the emergency department. She had muscle weakness and numbness, especially in the arms and hands for two months. Flaccid paralysis of the limbs was observed at the time of admission. She did not report vomiting, diarrhea, abdominal pain or drug use such as diuretics. There was no history of hypertension. None of her family had hypertension or sudden death at younger age. On physical examination, her blood pressure was less than 140/90 mmHg in repetitive measurements with a manual sphygmomanometer. Lower extremity motor strength was 2/5 and deep tendon reflexes were absent. Biochemical tests revealed that hypokalemia (2 mmol/L) with metabolic alkalosis (pH: 7.47 HCO3:30 mmol/L) and kaliuresis (24-h urinary potassium 87.89 mmol). Serum magnesium level and thyroid function tests were within the reference ranges. After the treatment of hypokalemia, neuromuscular symptoms regressed. Extremely high aldosterone levels (58.5 ng/dL) with suppressed renin activity (0.3 uIU/mL) were detected in blood tests. The diagnosis of PA was confirmed by unsuppressed aldosterone levels (44 ng/dL) after the saline infusion test. Adrenal contrast-enhanced CT identified a solid mass in the right adrenal gland which was 18×10 mm in size, consistent with adenoma (Figure 1). She was referred to surgery. Postoperatively, serum potassium and plasma aldosterone levels returned to normal without medication. Her home blood pressures remained between 110/70 and 120/80 mmHg.

Conclusion

Aldosterone-producing adenoma (APA) is one the most common cause of PA. In APA, aldosterone levels and blood pressures tend to be high. It has been reported that only 28% of patients with hyperaldosteronism have had hypokalemia and 3.1% may be normotensive. We described a patient with PA who presented with flaccid paralysis due to hypokalemia, moreover, she was normotensive. It is a rare condition for primary aldosteronism to present with hypokalemic paralysis. Delayed diagnosis and treatment can be life threatening.

In conclusion, we should consider primary aldosteronism in the differential diagnosis of severe hypokalemia and to keep in mind that patients may rarely be normotensive.
A different indication of pisphosphonates: Bone marrow edema
Authors: Çalışkan Mustafa , Kızılgül Muhammed , Bostan Hayri , Çakal Erman
Published: January 2023

Introduction

Bone marrow edema (BME) is an uncommonly diagnosed, reversible condition most often affecting the hip of middle-aged men. BME is characterized clinically by the onset of disabling bone pain, usually at a single skeletal site, generally in the lower limbs and most often the hip. Diagnosis is often delayed. The increased bone turnover and low bone mineral density may indicate a potential role for bisphosphonate therapy in BME. There is some evidence of the successful use of intravenous bisphosphonates in the treatment of BME of the hip. We aimed to present two cases of BME that were successfully treated with bisphosphonates.

Clinical Case

1: A 41-year-old male patient presented with left inguinal pain. His past medical history was unremarkable. The visual analog scale (VAS) was 8–9. On physical examination, there was a limited range of motion (ROM) on the left hip. Laboratory results were within normal limits. Non-contrast MRI revealed signal intensity changes consistent with BME in the left femoral head and neck of the femur, which was hypointense in T1W sections and hyperintense in T2W sections. With assisted mobilization, 3 mg IV ibandronic acid, calcium and vitamin D replacement was started. Pain control was achieved one week after bisphosphonate infusion. Complete resolution of bone marrow edema was seen in the MRI taken 2 months later (Figure 1). Bisphosphonate treatment with alendronate was completed for one year.

Clinical Case

2: A 59-year-old male patient presented with right hip pain that limits his walking. He was diagnosed with BME and avascular necrosis as a result of clinical and radiological evaluation in the center he applied and he underwent a right femoral core decompression operation. He was evaluated in our clinic due to ongoing pain and limitation of movement 5 months after the operation. On physical examination, there was limited ROM on right hip. All the results of laboratory tests were normal. MRI revealed signal changes consistent with bone marrow edema in the right femoral head and neck of the femur, which was hypointense in T1W sections and hyperintense in T2W sections. With assisted mobilization, 3 mg IV ibandronic acid, calcium and vitamin D replacement was started. Pain control was achieved 10 days after bisphosphonate infusion, and he returned to working life 1 month later. Complete resolution of the BME was observed in MRI performed 10 weeks later. Completion of the bisphosphonate treatment with alendronate for 1 year was planned.

Conclusion

The hip is the most frequently involved joint, with diffuse BME pattern in the femoral head and intertrochanteric region observed on MRI. BME may be a precursor to avascular necrosis when the diagnosis is delayed or the treatment is not well managed. Therefore, optimal timing of medical intervention is very important. Treatment with bisphosphonates is an effective and safe treatment. Additionally, providing early mobilization may prevent the risk of avascular necrosis and the workforce loss.
Progressive height increase in an adult patient: Aromatase Deficiency
Authors: Akçay Seçkin , Yavuz Dilek
Published: January 2023

Introduction

Aromatase deficiency (AD) is a rare autosomal recessive disease in that androgens are not converted into estrogens due to the CYP19A1 gene mutation. As estrogen deficiency is predominant, it is easier to diagnose females presented with ambigus genitalia, virilization and lack of secondary sexual characteristics during puberty. Diagnosis of aromatase deficiency is challenging in male patients. Male subjects usually present with bone and metabolic abnormalities. Here, we present a 31-year-old patient with a late diagnosis of aromatase deficiency.

Clinical Case

A 31-year-old male, medical doctor, was admitted to the Marmara University endocrinology outpatient clinic with a 5 cm progressive increase in height within 6 years, also complain of bone pain and cramps. Family history reveals born with ambiguous genitalia, etiology was not detected and she is followed up with oral contraceptive pills. In physical examination, his height was 193 cm and weight was 103 kg. He had eunuchoid body habitus. Secondary sexual characteristics were normal. Laboratory tests revealed that FSH:25.3 IU/l (1.5–12.4), LH:11.7 IU/l (1.7–8.6), total testesterone:957 ng/dl (249–836), E2<5 ng/l (11.3–43.2), DHEA-S:793 µg/dl (160–449), 17-OH progesterone:2.82 µg/l (0.5–2.1), Prl:7 µg/l (4.04–15.2), osteocalcin:44.1 ng/ml (9–42), Ca:9.7 mg/dl (8.8–10.5), P:3.3 mg/dl (2.5–4.5), ALP:208 U/l (33–98), PTH:12.7 µg/l (15–65), 25-OH vitamin D:29.3 µg/l, AST:47 U/l (10–37), ALT:40 U/l (10–37).

Bone survey demonstrated that bilateral humerus, radius, ulna, femur, tibia and fibula epiphyses were still unfused, bilateral genu varum, bilateral hallux valgus, scaphocephaly, scoliosis (Fig 1). Bone densitometry results were in osteoporotic range BMD at the femoral neck was 0.684 g/cm2, Z score was -2.6 and at the lumbar spine was 0.895 g/cm2, Z score was -2.

An incidentaloma (12×6 mm) detected in the right adrenal gland and testicular dimensions in scrotal ultrasound were normal. 1 mg DST was 0.24 µg/l, 24-hour urine metabolites were in the normal range, so it was evaluated as non-functional adenoma.

In the genetic analysis, homozygous exon 6 deletion was detected in the CYP19A1 gene. Genetic counseling was recommended for CYP19A1 gene mutation. Since liver function tests were elevated mildy, 12.5 μg transdermal estradiol was started. Androgens follow-up and bone survey 1 year later were planned.

Conclusion

AD should be kept in mind progressive height increase in adults other than gigantism. Since estrogen is essential for epiphysis fusion, bone health, fat and carbohydrate metabolism, estrogen treatment should be initiated as early as possible before bone and metabolic abnormalities develop.
Very high parathormone levels may not always be due to primary hyperparathyroidism
Authors: Pekkolay Zafer , Ülük Bermal
Published: January 2023

Introduction

Secondary hyperparathyroidism is a disease characterized by parathyroid gland hyperplasia originating from a localization other than the parathyroid gland. Common causes of this condition are kidney failure and vitamin D deficiency. Here, we presented a case of secondary hyperparathyroidism to sleeve gastrectomy.

Clinical Case

A 46-year-old female patient who applied to an external medical center with fatigue, weight loss, and muscle and joint pain was referred to our clinic with a diagnosis of primary hyperparathyroidism. In the examinations of the patient, PTH 455 pg/mL (normal range 15–65 pg/mL), 25-hydroxy vitamin D 4,95 uq/L, Ca total 8,8 mg/dL (normal range 8,5–10,5 mg/dL), phosphorus 7,4 mg/dL (normal range 2,5–4,5 mg/dL), Ca 24h urine 9,5 mg/day. No anomaly was detected in the neck USG imaging of the patient. In the detailed history, it was learned that a sleeve gastrectomy was performed in December 2016. It was understood that the PTH level was well above normal due to insufficient vitamin D absorption, leading to secondary hyperparathyroidism. We made a treatment plan for the patient diagnosed with secondary hyperparathyroidism. For six weeks, the patient was given cholecalciferol, 50,000 IU per week. Treatment was continued with daily maintenance of 2,000 IU. During the follow-up of the patient, parathormone levels reached normal values.

Conclusion

After sleeve gastrectomy, vitamin and mineral deficiencies are frequently encountered due to malabsorption. Very high parathormone levels may not always be due to primary hyperparathyroidism. Vitamin D deficiency can sometimes raise parathormone levels too high.
Mucopolysaccharidosis type 4 (Morquio syndrome): A case report
Authors: Akçay Seçkin , Akagündüz Fırat , Ölmez Osman , Öztürk Hişmi Burcu , Gözü Hülya
Published: January 2023

Introduction

Mucopolysaccharidosis (MPS) IVA (Morquio syndrome) is a rare lysosomal storage disease, that is caused by a deficiency in the enzyme N-acetylgalactosamine-6-sulfatase (GALNS) due to an autosomal recessive mutation in the GALNS gene. Herein, we present a MPS IVA case without regular follow-up, whose enzyme replacement was planned to start at age 30 for the first time, so as to attract attention to this rare disease.

Clinical Case

A 30-year-old female patient diagnosed with MPS IVA, that was evaluated due to corneal clouding referred to the Marmara University endocrinology outpatient clinic for enzyme replacement. On admission, she complains of impaired vision, hearing loss, hypoglycemic symptoms and numbness of hands and feet. While she was normal for about 2 years after birth, she was noticed for delays in crawling and walking from 2–3 year of age. However, she had definitive diagnosis of MPS-IVA at the age of 9 years, with low enzymatic analysis and genetic mutation in the GALNS gene located on chromosome 16q24.3. She operated on for bilateral glaucoma and cerebellar mass when she was 17. Her parents were third degree consanguineous, and she had one healthy younger brother. On physical examination, blood pressure: 99/67 mmHg, pulse: 72/min, temperature: 36°C, SpO2:99. She was in a wheelchair. Her height was 92 cm, weight was 30 kg, BMI: 25.6 kg/m2. Disproportionate short stature, coarse facial features, hypertelorism, genu valgum, pectus carinatum, kyphoscoliosis, were detected. Her neuromotor development was normal. Laboratory findings were unremarkable except for vitamin D hypovitaminosis. Radiographic findings were dysostosis multiplex, include abnormally shaped vertebral bodies with anterior beaking, posterior scalloping, platyspondyly and dens hypoplasia, thoracolumbar kyphosis, short, broad metacarpals, acetabular dysplasia, genu valgum, pectus carinatum, paddle-shaped ribs and short, and thick clavicles (Fig 1). Bone densitometry results were in osteoporotic range BMD at the femoral neck was 0.491 g/cm2, Z score was -2.8 and at the lumbar spine was 0.707 g/cm2, Z score was -3.6. She continued the 6-min walk test with the help of a walker and knee pad for 2.37 minutes and walked 3.4 meters. Echocardiography demonstrated that ejection fraction was 65%, normal left ventricular systolic function, no ventricular segmental wall motion defect, aortic 3 cusps, mild to moderate aortic valvular regurgitation, mild mitral valvular regurgitation. Pectus carinatum was detected on thorax CT imaging, whereas a restrictive disease pattern was not observed in PFT and DLCO. Bilateral severe mixed hearing loss was detected. Recombinant human GALNS (elosulfase alfa), 2.0 mg/kg/week, was planned to administer IV in 4 hr.

Conclusion

Because of the progressive nature of MPS- IVA, early diagnosis and early initiation of enzyme replacement therapy are critical to prevent cumulative systemic manifestations of the patient, especially the skeletal system.
Prolonged remission in latent autoimmune diabetes of adults (LADA): Is insulin resistance a major influence?
Authors: Rocha José Vicente , Alexandre Maria Inês , Gomes Ana Coelho
Published: January 2023

Introduction

Type 1 diabetes mellitus (T1DM) is a chronic inflammatory disease that courses with high serum glucose levels as a result of pancreatic beta cell destruction and subsequent insulinopenia. LADA is a type of autoimmune diabetes where damage to the beta cell occurs much slower. The natural history of type 1 diabetes is very heterogeneous and variable. This is especially true for LADA with several possible different clinical courses due to a wider variety of pancreatic cell destruction and insulin resistance. Clinically overt diabetes ensues when more than 80% of pancreatic cell mass is loss. After treatment initiation partial disease remission is common, especially in children. However complete remission is rare, and remission lasting for over a year is even rarer, with few reports published in literature. Some agents such as vitamin D and DPP4 inhibitors have been presented has having potential immunomodulatory effects.

Clinical Case

A 36-year-old man with grade 1 obesity (BMI 33 kg/m2) presented at the emergency department with symptoms of insulinopenia (polyuria and polydipsia in the previous 3 months) and hyperglycemia (capillary blood glucose >500mg/dL). Ketonemia was negative and pH was normal on blood gas analysis The diagnosis of diabetes mellitus was made and insulin therapy was instituted on a basal-bolus regimen. At the first follow-up appointment, due to his morphotype and familiar history of type 2 diabetes (mother diagnosed at 52 years of age), he stopped short-acting insulin and was started on metformin and SGLT2 inhibitor. A week later he was admitted in the hospital in euglycemic ketoacidosis. Initial workup revealed positive anti-GAD 41.8 U/mL, HbA1C 9.8%, C-peptide 1.83 ng/mL, serum insuline 17.4 uU/mL. Consequently, metformin and SGLT2 inhibitor therapy was stopped, and the patient resumed basal bolus insulin regimen. He then remained under a basal insulin without need of meal-time insulin bolus, progressively lowering the basal insulin dose until suspension four months later. Simultaneously, lifestyle changes were implemented with significant weigh loss (BMI 33 > 26.4 kg/m2 at the time of insulin suspension). After 3 years of follow-up the patient remains without need of antidiabetic therapy, with normal Hba1c 5.3%. Anti-GAD antibodies remain positive (39.4 U/mL) but C-peptide and serum insulin are within the reference range (1.69 ng/mL [1.1–4–4], 6.9uU/mL [2.6–25], respectively).

Conclusion

Prolonged disease remission in type 1 diabetes is rare. This case highlights an especially long “honeymoon” period in a patient with LADA. Obesity and insulin resistance probably played a role in the initial patient presentation, and its improvement probably helps to justify this prolonged remission. In spite of the family history of diabetes, other types of diabetes seem unlikely due to positive antibodies and SGLT2 inhibitor associated euglycemic ketoacidosis.
Successful treatment of a case of Congenital Lipodystrophy with 1 mg subcutanous Semaglutide
Authors: Almudhammed Rana Abdulsalam
Published: January 2023

25-year-old female presented to the endocrine clinic suffering from uncontrolled blood sugar and irregular period, she was diagnosed with type 1 diabetes since she was 15 and treated with premixed insulin, on the other hand she was diagnosed with polycystic ovary syndrome and treated with oral contraceptive pills, on examination; there is acanthosis nigricans in the axilla and forearm, android lean body habitus and acromegalic face, hirsutism and prominent veins. Labs revealed high triglyceride (more than 1000 mg/dL), high fasting insulin, high total testosterone 0.9 ng/mL, HbA1c 14,5%, high ALT, albuminuria, she is using very high doses of insulin yet uncontrolled, we diagnosed her as generalized lipodystrophy, the drug of choice is metroleptin which is not available, so I started pioglitazone 45 mg with semaglutide 1mg, gradually weaned off insulin. After 3 months of treatment her HbA1c declined to 7 without insulin, triglyceride to 422 mg/dL, proteinuria declined but was not normalized. We postulate the hypothesis that the insulin sensitizing properties of GLP1 agonist in the treatment of insulin resistance syndromes can be implemented particularly in countries with middle and low socioeconomic status that don't have access to the expensive drugs.

Figure 1. Patient footage oral consent taken.  Table 1.Results of biochemical parameters before and after treatment.
New-Onset Type 1 Diabetes Mellitus (T1DM) in a Pediatric Patient with Beckwith-Wiedemann Syndrome
Authors: Ehsan Lubaina , Anz Reem , Asebes Hannah , Longmire Berrin Ergun
Published: January 2023

Introduction

Beckwith-Wiedemann Syndrome (BWS) is the most common overgrowth syndrome with up to 50% of infants found to have hypoglycemia which has been believed to be related to hyperinsulinemia. However, our case report highlights a patient with the unusual presentation of concurrent BWS and T1DM along with the discussion of genetic factors that may contribute to the pathogenesis.

Clinical Case

We present the case of a 4-year-old African American female with a past medical history of BWS, twin gestation, prematurity, omphalocele, and patent ductus arteriosus. Her BWS had been diagnosed at birth via genetic testing which found a loss of methylation on the maternal chromosome at imprinting center 2 (IC2) on chromosome 11. During her newborn period, she did not have hypoglycemia. She presented to her primary care physician with a 2.4-kilogram weight loss, new-onset headaches, polyuria, and polydipsia for three months. She also had a viral upper respiratory tract infection a month prior to presentation. Her twin sister did not have similar complaints. Her physical exam including vital signs was reassuring. With the concern for diabetes, further work-up was done which showed an elevated serum glucose level of 681 mg/dL, and hemoglobin A1C of 12.4%. She was admitted for new-onset diabetes. Further labs on admission also showed elevated transglutaminase IgG and positive glutamic acid decarboxylase 65 (GAD65) antibody (level: 444 nmol/L, normal: ≤0.02 nmol/L). Notably, no acidosis was detected in the initial investigations and, unfortunately, due to laboratory error the diabetes antibody panel was cancelled. She was started on a basal-bolus insulin regimen with the diagnosis of new-onset T1DM without ketoacidosis.

BWS does not have T1DM as a known characteristic. Hypoglycemia secondary to hyperinsulinemia rather than the opposite, such as our case, is associated with BWS. Due to this, our case is rare, and we found a case report from Europe describing a similar phenomenon. Our patient had a GAD65 antibody being positive which explains having T1DM although there are no studies showing the association of BWS with a positive GAD65 antibody. Our patient also had a viral infection prior to the diagnosis of T1DM which may have triggered autoimmunity. Further, IC2 loss of methylation present in our patient regulates the expression of CDKN1C which has been previously reported to be associated with diabetes.

Conclusion

Further studies will be required to identify the possible case of T1DM in a patient with BWS. We plan on obtaining a diabetes antibody panel to further assess the genetics of our patient.
Hypothalamic involvement of sarcoidosis presenting with behavioral disorder
Authors: Erbatur Nuriye Hale , Koç Gönül , Mehlika Kuşkonmaz Şerife , Çulha Cavit
Published: January 2023

Introduction

Sarcoidosis is an idiopathic, chronic, disease with non-caseating granuloma formation. Central nervous system (CNS) involvement (neurosarcoidosis) is observed in 5–15% of cases. Hypothalamic–pituitary (HP) neurosarcoidosis (NS) accounts for 0.5% cases of sarcoidosis. We present a case of hypothalamic-pituitary sarcoidosis with compulsive behaviors, diabetes insipidus and pan-hypopituitarism.

Clinical Case

A 43-year-old male patient was admitted to our clinic with complaints of fatigue, polydipsia, erectile dysfunction for 1 month, as well as compulsive behaviors such as excessive shopping, exercise and hyperphagia. In his history, it was learned that he had been diagnosed with sarcoidosis 1 year ago, based on skin biopsy and clinical examination, and discontinued the treatment. On physical examination, erythematous lesions were observed on the face and back. Multiple lymphadenopathies (LAP) of 2 cm in size were palpated in the axilla and inguinal region. The patient's neurological examination was normal. MRI of the brain showed heterogeneous enhancement of the gland parenchyma posteriorly. In sagittal sections, an area that is not contrasted to the gland base is selected. (Fig. 1) The infundibulum is markedly thick and shows enhancement, and in its continuity, similar thickening and enhancement are observed in the hypothalamus. Due to the thickening of the infundibulum, the optic chiasm appears to be spread on both sides. Differential diagnosis was TB, sarcoidosis and lymphoproliferative disease.

Pituitary function showed free T4 0.53 ng/ml (normal 0.93–1.7), TSH 0,89 μIU/ml (normal 0.27–4.2), FSH 0.87 milliunit/ml (normal 1–11), LH <0.55 milliunit/ml (normal 1–8), ACTH 1,5 pg/ml (normal 7.2–63), Cortisol 3,59 μg/dl Prolactin 14.3 ng/ml (normal 0.5–17), total testosterone 2,5 ng/ml (normal 37–198). He tested negative for ANA, HIV, Hepatitis C, Mycobacterium TB Interferon-Gamma. The patient underwent skin biopsy and excisional lymph node biopsy. Non-necrotizing granulomas found at biopsy samples. He was started on desmopressin, methylprednisolone, levothyroxine. Patient had significant improvement following treatment.

Conclusion

Neurosarcoidosis may present with various clinical features depending on the anatomical location of the disease. Hypogonadotropic hypogonadism, diabetes insipidus, amenorrhea and anterior pituitary insufficiency are the most common endocrine findings. Hypothalamic findings such as changes in thirst, disturbance in thermoregulation, changes in appetite and body weight without diabetes insipidus have been reported in case reports. Although it is a rare condition, symptoms of hypothalamic-pituitary changes, can be seen in sarcoidosis and are an indication for treatment. It requires long-term management by a multidisciplinary team of patients.
Sustained hypercortisolemia after bilateral adrenalectomy in Cushing's disease
Authors: Muradov Ilkin , Kara Zehra , Uysal Serhat , Demir Ahmet Numan , Sulu Cem , Kadioglu Pinar
Published: January 2023

Introduction

Cushing's disease caused by pituitary corticotropin (ACTH)-secreting tumors. These tumors are almost always benign and are usually microadenomas. In 30 to 40 percent, the microadenoma is so small that it is not detectable by magnetic resonance imaging (MRI). Primary therapy consists of transsphenoidal surgery or pituitary irradiation. Patients who fail this first approach can be treated either by repeat transsphenoidal surgery, medical therapy, radiotherapy, or, as a final resort, surgical or medical adrenalectomy.

Clinical Case

A 38-year-old male patient presented with headache and fatigue. The laboratory examinations reviewed ACTH depending Cushing's syndrome. A suspicious lesion in the pituitary with no contrast enhancement was observed in Sella MRI. Cavernous sinus sampling consistent with central sources. He was operated in 2018 for pituitary Cushing's disease. Reticulin framework disrupted compatible with adenoma but, ACTH could not be stained in immunohistochemical staining for technical reasons. Due to the high cortisol levels of the patient in the postoperative follow-up, the patient underwent bilateral adrenalectomy in 2019.

Because of active Cushing's disease, patient was re-evaluated in 2022. In laboratory examinations, HGB 16.6 g/dL, WBC 6400 /uL, NEU 3200 /uL, PLT 228000 uL, cre 0.76 mg/dL, TSH 1.5 mIU/L, FT4 1.2 ng/dl, FSH 4.6 U/L, LH 7.98 U/L, PTH 23.7 ng/L, PRL 17 µg/L, Total Testosterone 571 ng/dl, Progesterone 0.06 µg/L, GH 0.04 ug/L, IGF1 83 µg/L were detected. Basal cortisol was 35 ug/dl and ACTH 67 ng/L. Cortisol with 1 mg of DST resulted in 28 ug/dl. 2 mg DST resulted in cortisol 38 ng/L. Free cortisol in the urine was found to be 281 mg/day (n<130 mg/day). Empty sella was observed in sella MR. No prominent contoured lesion was observed in the pituitary gland. Adrenal gland was not observed in the Abdominal MRI. No tumor was detected in Thorax CT.

The patient's pasireotide 0.3 mg 1×1 treatment was continued. Metyropane 250 mg 2×1 was added to the treatment.

Conclusion

In Cushing's disease, the ACTH-secreting adenoma may be too small to be detected.
Difficulties in diagnosing acromegaly, acromegaly with apparently normal GH: Micromegaly
Authors: Demir Ahmet Numan , Kara Zehra , Sulu Cem , Kadiıoglu Pinar
Published: January 2023

Introduction

Acromegaly results from pathologically increased secretion of growth hormone (GH) from the pituitary somatotroph adenoma. If left untreated, it is associated with increased morbidity and mortality. We present a case of micromegaly, whose diagnosis is challenging for clinicians.

Clinical Case

A 40-year-old woman presented with complaints of enlarged facial features, hands and feet, and separation between teeth. She was using a salbutamol inhaler with the diagnosis of asthma. Her physical examination was unremarkable except for a body mass index of 28.7 kg/m2 and malocclusion. Insulin-like growth factor (IGF)-1 250 ng/mL (101–234) and GH 2.1 ng/mL was detected. 0, 1. and 2nd hour in oral glucose tolerance test (OGTT)-GH; hour GH/glucose values were 6.7/70, 1.5/98, 0.35 ng/ml /95 mg/dl, respectively. Sella magnetic resonance imaging (MRI) revealed an 8×5mm adenoma in the pituitary gland (Figure). Pseudoacromegaly causes such pachydermoperiostitis, severe insulin resistance, familial mandibular prognathism, use of phenytoin and minoxidil, and causes of false IGF-1 elevation such as pregnancy, puberty/adolescent period, thyrotoxicosis, glucocorticoid use were excluded. It was decided that the patient should be operated on. No adenoma was detected in the pathology tissue of the operated patient, but IGF-1 was detected at 201 ng/ml (101–234) and GH was 1,1 ng/ml in the 3rd postoperative month. The nadir GH was found to be 0.3 ng/ml in the OGTT-GH suppression test. Medical treatment was not started. The case has been followed for 2 years in remission.

Conclusion

Micromegaly describes a subset of patients with clinically evident acromegaly and elevated IGF-1 with apparently normal basal GH and often <0.4 ng/mL glucose suppressed GH. This condition is relatively rare in patients with acromegaly. As in our case, micromegaly should be considered in diagnosing patients with “normal” GH but with clinical signs, or even patients without clinical signs but with pituitary tumors and elevated IGF-1.
GH-Producing pituitary adenoma and concomitant Rathke's cleft cyst: A case report
Authors: Yaman Kalender Derya Sema , Gölbaşı Murat , Ertürk Mehmet Sercan , Çavdar Ümit , Örük Güzide Gonca , Duygulu Gökhan , Önder Pamuk Barış
Published: January 2023

Introduction

Rathke cleft cysts (RCCs) are commonly believed to be cysts formed from remnants of Rathke's pouch. It is usually asymptomatic, < 3mm in diameter, and found in 13–33% of normal pituitary glands. The coexistence of pituitary adenoma (PA) and RCC is rare (incidence rate of 0.51%-1.7%), and growth hormone hypersecretion has also been observed in a limited number of cases in these patients. Therefore, we aim to present a rare case of growth hormone- (GH-) producing PA with concomitant RCC.

Clinical Case

A 29-year-old female patient, due to primary amenorrhea, was diagnosed as having 46XY chromosomal Swyer syndrome from her previous visit, and she had bilateral salphengoopherectomy afterward. In clinical follow-ups, due to the presence of growth complaints in the hands and feet, insulin-like growth factor-1 (IGF-1) was found to be high. The basal serum GH value was 8.89 ng/mL, and IGF-1 was 369 ng/mL. The 75 gr oral glucose tolerance test (OGTT) result showed that the serum GH level was not suppressed below 1.0 μg/L, and the test was repeated twice. Other anterior pituitary hormone axes are normal. In the pituitary magnetic resonance imaging revealed a low-signal 4 mm Rathke cleft cyst is observed in the T1A image in the midsection of the pituitary gland and a high-signal intra-cystic nodule is observed within the cyst on the T1A image (Figure 1A). The fluid-fluid level is observed in the cyst on the T2A image (Figure 1B).

Conclusion

The relationship between RCC and PA is unclear and theoretical. The theory is “transitional pituitary tumor,” defined as the Rathke pouch forming the anterior lobe of the pituitary gland with a proliferation of the anterior wall. Moreover, PAs originate from the anterior lobe of the pituitary gland via clonal changes. This shows that RCCs originated from the remnant of the Rathke pouch, and PA has a common embryonic origin. Nevertheless, they rarely occur at the same time. Only 14 patients with GH-producing PA and concomitant RCC have been reported in the literature. Preoperative correct diagnosis of PA and RCC coexistence is difficult, because RCCs’ imaging characteristics (size, position, and intensity) are highly variable, and cystic degeneration occurs in 5% to 18% of PA cases. RCCs are often surrounded by the normal pituitary gland and are located in the nearby midline of the sellar region. MRI characteristics of sellar lesions for PAs existing concomitant with RCCs may present with variable intensity on T1-weighted imaging. If radiographic imaging shows that typical RCC and PA are not obvious at first glance, the possibility of concomitant PA still needs to be considered. If the PA in this patient had been nonfunctional, correct diagnosis of the concomitant PA would have been much more difficult. This case offers a reminder that although rare, RCC can accompany PA, and performing contrast-enhanced MRI is useful to detect RCC.
A detailed pituitary profile always matters
Authors: Helmy Assaad Khalil Ramy Samir
Published: January 2023

29-year-old female with known hypothyroidism and positive thyroid auto antibodies, followed up throughout pregnancy for adjusted doses of thyroid replacement therapy, presented 2 months post-partum with gradually increasing fatigue, repeated pre-syncope experience, inability to cope with daily home and family needs and headache.

Adequacy of thyroid replacement therapy was questioned, TSH has been performed: 0.18 mIU/ml.

Checking the blood pressure in lying and standing position has showed Postural hypotension. An urgent measurement of Cortisol (am) showed a result of1.06 ug/dl.

Preliminary Differential Diagnoses have been suggested; Pituitary apoplexy, Pituitary adenoma, Autoimmune adrenalitis (Autoimmune Polyglandular Syndrome) or Others.

On further detailed history, the patient affirmed dizziness and fainting liability on standing from lying position, bitemporal headache more in the morning. However, she denied frequent urination throughout the day, neither repeated times at night. In addition, she confirmed efficient breast feeding.

Continued Lab investigations:

ACTH (am) (Low); FT4 (Low; on replacement therapy); IGF1 (Normal)

Serum osmolality (Normal); Urine osmolality (Normal); E2 / LH / FSH (normal physiological levels)

Prolactin (normal for breast feeding)

MRI pituitary and sella: Diffuse isointense enlargement of anterior pituitary gland. Homogenous and strong diffuse pituitary enhancement with gadolinium contrast.

History and investigations were not fully matching with any of the previously proposed differential diagnoses, especially in regards of selective corticotroph and thyrotroph affection, sparing other pituitary cell types. Moreover, the autoimmune predisposition, the nature of the clinical presentation and its timing during early postpartum period, together with the laboratory and imaging investigations were all matching with the diagnosis of Lymphocytic Hypophysitis.

The Patient got pregnant again 14 months post-partum, reflecting spared gonadotroph function and highlighting the importance to identify this uncommon diagnosis and to notify the patient about normal gonadal function and the normal possibility of pregnancy.

However, she remained on hydrocortisone and thyroxine replacement. Finally, it is important that this condition should not be misdiagnosed in the first place as postpartum thyroid disturbance and TSH results, especially during and after pregnancy, shall always be interpreted in the clinical context and with the overall thyroid profile.
A case of primary ovarian failure with Nijmegen Breakage a chromosomal instability syndrome
Authors: Elif Boncukçuoğlu Ayşe , Akçay Seçkin , Üstay Özlem
Published: January 2023

Introduction

Nijmegen Breakage Syndrome (NBS) is a rare autosomal recessive chromosomal instability syndrome, characterized by dysmorphic facial features, intrauterine growth retardation and short stature, recurrent sinopulmonary infections, combined immune deficiency, radiosensitivity, increased risk for cancer, as well as premature ovarian failure. Nibrin gene mutation is responsible for the pathogenesis of the disease. The mechanism of gonadal failure in NBS is thought to be meiotic arrest in gametocytes.

Clinical Case

A 23-year-old female was admitted to the Marmara University endocrinology outpatient clinic because of secondary amenorrhea. Her first menarche occurred spontaneously at the age of 13, but she has never bled again afterwards. In physical examination, blood pressure was 109/68 mmHg, pulse was 80/min, and temperature was 36°C. Her height was 163 cm, and weight was 67 kg, BMI: 25.6 kg/m2. Midfacial prominent appearance, micrognathia, microcephaly was observed. Breast was assessed for II stage in Tanner scale. Ferriman–Gallwey score was 5. Psychomotor development was natural, cognitive dysfunction was not observed. Her three siblings and aunt had a history of infertility, also her parents were third degree consanguineous. The patient stated that she had recurrent sinopulmonary infections and used several antibiotics since childhood. However, there was no hospitalization due to infection by now. Her two older sisters died due to cancer when they were 10 and 21 years old. The patient had primary ovarian insufficiency according to elevated serum gonadotropins concentration and low serum estradiol concentration (Table 1). The uterus was 50 mm in size, its contours were smooth, and the echo of myometrium was diffusely homogeneous. Bilateral ovaries were not observed in the suprapubic pelvic US examination. Karyotype analysis was performed that was found 46, XX. When considering her family history, facial dysmorphic appearance, and findings of primary ovarian failure, genetic analysis revealed NM_001024688.2 c.625C>T(p.Q209*) homozygous mutation. The patient was started on hormone replacement therapy (estrogen 2 mg once daily, dydrogesterone 10 mg once daily) after the diagnosis. Genetic counseling, immunodeficiency and malignancy screenings were performed. Interestingly, despite the history of recurrent infection, total Ig levels and vaccine responses were normal. Although no malignancy was observed in our case, it is noteworthy that two older sisters died due to cancer. It was recommended to continue the annual screenings.

Conclusion

Family history should be thoroughly questioned in patients presenting with hypogonadism. NBS should be kept in mind as a rare cause in the presence of a typical phenotypic appearance, recurrent infections, and a family history of infertility and malignancy.
Primary Aldosteronism and COVID-19-related Management, Disease Severity, and Outcomes: A Retrospective Cohort Study
Authors: Thomas Teressa S , Walpert Allie R , Shen Grace , Dunderdale Carolyn , Srinivasa Suman
Published: January 2023

Context

The SARS-CoV-2 virus is dependent on components of the renin-angiotensin-aldosterone system for infectivity. Primary aldosteronism (PA) is a form of secondary hypertension mediated by autonomous aldosterone production. The intersection of COVID-19 and PA, both which may involve components of the renin-angiotensin-aldosterone system, remains unknown.

Methods

We assessed PA as a risk factor for COVID-19 infection and compared management, severity of disease, and outcomes during COVID-19 with a matched population of patients with essential hypertension (EH) by conducting a retrospective observational cohort study.

Results

Of the patients with PA, 81 had a negative PCR test for COVID-19, whereas 43 had a documented positive PCR test for COVID-19. Those patients with PA who tested positive for COVID-19 tended to be female (P = .08) and the majority of those with COVID-19 infection identified as non-White race (P = .02) and Hispanic ethnicity (P = .02). In a subanalysis, 24-hour urine aldosterone on initial PA diagnosis tended to be higher those in the PA group who developed COVID-19 compared with those in the PA group who did not develop COVID-19 [median (interquartile range): 36.5 (16.9, 54.3) vs 22.0 (15.8, 26.8) mcg, P = .049] and was an independent predictor of COVID-19 infection controlling for sex, race, and ethnicity. Angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, and mineralocorticoid receptor antagonist use did not differ between those patients with PA who did and did not have COVID-19 infection. Comparing those patients with PA and matched patients with EH (n = 286) who were COVID-19 PCR positive, there was a significantly higher incidence of cardiovascular complications (12 vs 2%, P = .004) in the PA vs EH group.

Conclusion

These data begin to inform us as to whether PA should be a newly identified subpopulation at risk for COVID-19-related cardiovascular disease sequelae.
Holding time has limited impact on constitutive innate immune function in a long-lived Antarctic seabird, the Adélie penguin: implications for field studies
Authors: Hicks Olivia , Kato Akiko , Wisniewska Danuta M. , Marciau Coline , Angelier Frédéric , Ropert-Coudert Yan , Hegemann Arne
Published: January 2023

There is great interest in measuring immune function in wild animals. Yet, field conditions often have methodological challenges related to handling stress, which can alter physiology. Despite general consensus that immune function is influenced by handling stress, previous studies have provided equivocal results. Furthermore, few studies have focused on long-lived species, which may have different stress-immune trade-offs compared to short-lived species that have primarily been tested. Here, we investigate whether capture and handling duration impacts innate immune function in a long-lived seabird, the Adélie penguin (Pygoscelis adeliae). We found no evidence for changes in three commonly used parameters of innate immune function upon holding time of up to 2 h, suggesting that immune function in this species is more robust against handling than in other species. This opens up exciting possibilities for measuring immune function in species with similar life-histories even if samples cannot be taken directly after capture.
Parental exposure to ocean acidification impacts gamete production and physiology but not offspring performance in Nematostella vectensis
Authors: Glass Benjamin H. , Schmitt Angela H. , Brown Kristen T. , Speer Kelsey F. , Barott Katie L.
Published: January 2023

Ocean acidification (OA) resulting from anthropogenic CO2 emissions is impairing the reproduction of marine organisms. While parental exposure to OA can protect offspring via carryover effects, this phenomenon is poorly understood in many marine invertebrate taxa. Here, we examined how parental exposure to acidified (pH 7.40) versus ambient (pH 7.72) seawater influenced reproduction and offspring performance across six gametogenic cycles (13 weeks) in the estuarine sea anemone Nematostella vectensis. Females exhibited reproductive plasticity under acidic conditions, releasing significantly fewer but larger eggs compared to ambient females after 4 weeks of exposure, and larger eggs in two of the four following spawning cycles despite recovering fecundity, indicating long-term acclimatization and greater investment in eggs. Males showed no changes in fecundity under acidic conditions but produced a greater percentage of sperm with high mitochondrial membrane potential (MMP; a proxy for elevated motility), which corresponded with higher fertilization rates relative to ambient males. Finally, parental exposure to acidic conditions did not significantly influence offspring development rates, respiration rates, or heat tolerance. Overall, this study demonstrates that parental exposure to acidic conditions impacts gamete production and physiology but not offspring performance in N. vectensis, suggesting that increased investment in individual gametes may promote fitness.
Accounting for the expansion of the universe using an energy/momentum model to construct the space-time metric
Authors: James Hugh
Published: January 2023

Background: The success of the theories of special and general relativity in describing localised phenomena, such as objects undergoing high speed motion or located in gravitational fields, needs no further elaboration. However, when applied to the evolution of the universe several problems arise which can require an additional model, e.g., inflation during the early expansion, and adjustments to parameters to account for phenomena such as the late-time acceleration of the universe.

Methods: Focusing on the difference between the ways in which space and time are measured, this paper shows that there are two paths which allow the equations of special relativity to be produced from the same basic postulates.

Results: While the standard theory utilises the Minkowski metric, an alternate path is possible which uses an energy/momentum, or dynamic model which transforms the Minkowski metric into an Euclidean form by multiplying the coordinates by functions of γ (=(1-v2/c2 )-1/2) to derive a new space-time metric. When utilising this dynamic metric, the relativistic equations are unchanged for local phenomena such as the Lorentz coordinate transformation and the energy/momentum equation for high-velocity objects.

Conclusions: However, the derived metric alters the perceived overall structure of the universe in a manner that, for the simplest model under this system, allows the reproduction of observed cosmological features, such as the intrinsic flatness of the universe and the apparent late-time acceleration of its expansion, without the need of additional models or changes in parameter values.
Ensemble of multimodal deep learning autoencoder for infant cry and pain detection
Authors: Kristian Yosi , Simogiarto Natanael , Sampurna Mahendra Tri Arif , Hanindito Elizeus , Visuddho Visuddho
Published: January 2023

Background: Babies cannot communicate their pain properly. Several pain scores are developed, but they are subjective and have high variability inter-observer agreement. The aim of this study was to construct models that use both facial expression and infant voice in classifying pain levels and cry detection. 

Methods: The study included a total of 23 infants below 12-months who were treated at Dr Soetomo General Hospital. The the Face Leg Activity Cry and Consolability (FLACC) pain scale and recordings of the baby's cries were taken in the video format. A machine-learning-based system was created to detect infant cries and pain levels. Spectrograms with the Short-Time Fourier Transform were used to convert the audio data into a time-frequency representation. Facial features combined with voice features extracted by using the Deep Learning Autoencoders was used for the classification of infant pain levels. Two types of autoencoders: Convolutional Autoencoder and Variational Autoencoder were used for both faces and voices. 

Result: The goal of the autoencoder was to produce a latent-vector with much smaller dimensions that was still able to recreate the data with minor losses. From the latent-vectors, a multimodal data representation for Convolutional Neural Network (CNN) was used for producing a relatively high F1 score, higher than single data modal such as the voice or facial expressions alone. Two  major parts of the experiment were: 1. Building the three autoencoder models, which were autoencoder for the infant’s face, amplitude spectrogram, and dB-scaled spectrogram of infant’s voices. 2.  Utilising the latent-vector result from the autoencoders to build the cry detection and pain classification models.   

Conclusion: In this paper, four pain classifier models with a relatively good F1 score was developed. These models were combined by using ensemble methods to improve performance, which resulted in a better F1 score.
A case for vaccinating adolescent girls for protection against COVID-19 during pregnancy and childbirth in resource-limited settings
Authors: Blakeway Helena , Hookham Lauren , Nakabembe Eve , Koech Angela , Khalil Asma , Ladhani Shamez , Temmerman Marleen , Le Doare Kirsty
Published: January 2023

The coronavirus disease 2019 (COVID-19) pandemic has had severe implications worldwide, including increased adverse maternal and neonatal health outcomes. Vaccination is one way of protecting against these adverse health outcomes. However, in some low-resource settings, vaccine inequity has led to poor uptake of COVID-19 vaccination. There are very high rates of adolescent pregnancy in low-resource settings, which are likely to become even higher as we begin to see the full effects of COVID-19 lockdown measures, including school closures. Although the benefits of COVID-19 vaccination in adolescents are debated, we propose that adolescent girls should be prioritised in COVID vaccination roll out in low-resource settings. This is to provide protection from severe COVID-19 disease in pregnancy, preventing adverse maternal and neonatal health outcomes.