Recurrent hypothermia, hypersomnolence, central sleep apnea, hypodipsia, hypernatremia, hypothyroidism, hyperprolactinemia and growth hormone deficiency in a boy – treatment with clomopramine

Abstract

A boy referred at the age of 4 years because of obesity and under observation for 16 years, was found to be suffering from a hypothalamic syndrome of unknown origin characterized by progressive obesity, polyphagia, deficiency of growth and thyroid hormone, hyperprolactinemia, hypodipsia, hypernatremia and hyperosmolality without diabetes insipidus. At ages 11 and 16 there were 3 day episodes of spontaneous muscular weakness, hypersomnolence and hypothermia associated with central sleep apnea and severe bradycardia. Subsequently, decreased ventilatory responsiveness to carbon dioxide (CO2) was found as a consequence of blunted neural drive. Therapy with clomipramine HCl (AnafranilR Ciba-Geigy) for 6 months led to a normalization of serum sodium levels, pulse rate, ventilatory response to dioxide with no recurrence of the central apnea within 4 following years.

Diagnosis and management of periodic hypothermia

“…In these patients, clonidine may be an effective agent for prophylaxis against further episodes (table). A periodic hypothermia syndrome with similar clinical characteristics to Shapiro syndrome has been reported in children with a normal MRI of the brain, in some cases referred to as episodic spontaneous hypothermia with hyperhidrosis (ESHH). [11][12][13][14][15][16] In these cases, children experience recurrent, spontaneous episodes of hypothermia below 35°C that last for hours, are associated with lethargy and diaphoresis, and terminate spontaneously with return to Dysfunction, injury, or destruction of the preoptic area, whether congenital or acquired, can lead to the development of periodic hypothermia.…”

Hypothalamic dysfunction in a child: A distinct syndrome?

“…In the same patient, amphetamine increased the level of activity of the child, but resulted in seizures and inappropriate ADH secretion. In one case, clomipramine therapy seemed to permanently normalize the ventilatory re-sponse to CO2 and to prevent apnoeic episodes, but did not improve the others problems [2]. Our patient also seemed to benefit, at least transiently, from clomipramine, but this apparent improvement may also be attributed to the natural course of the disease.…”

“…The absence of lesion was confirmed at autopsy. To our knowledge, only three similar cases have been described in the literature [1][2][3]; their main features, as well as those of our case are summarized in Table 1. We report the first girl affected by this syndrome.…”

“…We report a case of hypothalamic dysfunction of obscure origin in a 9-year-old girl and compare her features with those of three previously reported boys with similar problems [1][2][3].…”

“…A literature search revealed three similar cases [1][2][3], one of them apparently responding to clomipramine. On discharge, the referring physician was advised to start this medication and to wean the child from methylphenidate under close surveillance in the hospital.…”