Hypothalamic Dysregulation; A Hidden Culprit in Multiple Sclerosis Symptoms
Authors: Hernandez-Cordero Nicole Z , Rivera-Nieves Yadiel , Canales-Ramos Nicolle , Colon-Castellano Janet M , Grana-Santini Alberto J , Burgos-Ortega Nydia I , Feliciano-Emmanuelli Melba , Gonzalez-Rodriguez Loida A , Alvarado-Santiago Milliette , Ramirez-Vick Margarita 
Published: May 2021

Abstract
Background: A possible association between multiple sclerosis (MS) and dysregulation of hypothalamic-pituitary axis has been reported and its endocrine manifestations can be confused with many nonspecific symptomatology attributed to MS. We report such a case and present the improvement of symptoms independent of MS therapy.
Clinical Case: Case of a 45 years-old female with history of type 2 diabetes mellitus, dyslipidemia, HTN, obesity class I and MS that was evaluated for follow up with complaints of fatigue, weakness, somnolence and memory problems. No menstrual disturbances with regular cycles. Denies weight changes, anorexia, nausea, vomiting or abdominal discomfort. Previous hormonal workup showed normal levels of cortisol, ACTH, prolactin and TSH. Nonetheless, on repeated hormonal profile due to nonspecific complaints, patient was found with normal TSH (2.65 mIU/mL, 0.3-3.0 mIU/mL) and low free T4 (0.65 ng/dL, 0.78-2.19 ng/dL). Repeated thyroid function tests by equilibrium dialysis showed a borderline low FT4 (0.8 ng/dL, 0.78-2.19 ng/dL), despite a persistently normal TSH (2.26 mIU/mL, 0.3-3.0 mIU/mL). Suspecting hypopituitarism, a complete hormonal workup revealed a low normal serum cortisol in early morning of 8.39 mcg/dL and ACTH of 16.7 pg/mL, normal prolactin of 10.5 ng/mL and a first IGF-1 evaluation of 68.9 ng/mL, which was low for female age range (98-261 ng/mL). Due to concerns for possible complications during an insulin tolerance test, a cosyntropin stimulation test was performed with adequate peak cortisol response at 30.5 mcg/dL. Most recent brain MRI without pituitary protocol was remarkable for multiple bilateral demyelinating plaques compatible with MS diagnosis that also involved the left thalamus, although no other area adjacent to the hypothalamus or pituitary gland was described. The patient was subsequently started on levothyroxine replacement to a goal of free T4 at the upper normal range, with overall improvement in symptoms and quality of life. Growth hormone status and gonadal axis to be reevaluated. This case emphasizes the importance of clinical judgement and reminds us that overlapping symptoms can lead to misdiagnosis, particularly in conditions with nonspecific symptomatology as MS.
Conclusion: This is an unusual case of a patient with multiple sclerosis presenting with hypopituitarism suggesting the possibility of hypothalamic disturbance as the etiology. It has been proposed that demyelinating MS lesions in fiber bundles in and adjacent to the hypothalamus may compromise hypothalamic function. Mechanisms for fatigue in MS have been mostly associated with hyperactivity of HPA axis, not found in our patient. Hypothalamic dysfunction can be frequently overlooked due to overlapping symptoms with MS, despite being a treatable condition that can greatly improve quality of life in these patients.