One leading hypothesis concerning the mechanism of hyponatremia in these cases is secretion of another oligopeptide, atrial natriuretic factor (ANF) that is found mainly in the walls of the cardiac atria but also in neurons surrounding the third ventricle in the anteroventral hypothalamic region. ANF activity causes natriuresis. It physiologically opposes that of ADH in the kidney tubules and it also strongly inhibits ADH release from the hypothalamus (see review by Samson). Like some other neural peptides, ANF is secreted in bursts, and the natriuresis it produces may be evident only if total urinary sodium content is measured over many hours or days.
The role of ANF in causing the hyponatremia that follows subarachnoid hemorrhage is controversial (see Wijdicks et al and Diringer et al for opposing views), but it is our experience that the hyponatremia in this condition is the result mainly of salt loss, not water retention. Because fluid restriction after subarachnoid hemorrhage may precipitate cerebral ischemia from vasospasm, the proper approach is to maintain normal intravascular volume with intravenous fluids and to correct hyponatremia by infusion of normal saline.
In addition to head trauma, salt wasting has also been reported with cerebral tumors, after pituitary surgery, and in the dysautonomia of Guillain-Barré syndrome, conditions that have all also been associated with SIADH. As already stated, in each of these disorders, should the patient be hyponatremic, it is desirable to determine the intravascular volume and the urine sodium output before instituting treatment.
Other Disturbances of Antidiuretic Hormone and Thirst
Conditions have been described in which the osmoreceptor control of ADH and of thirst appear to be dissociated. As reported by Hayes and coworkers, rare patients have been reported to repeatedly developed severe hypernatremia (levels as high as 180 to 190 mEq/L), presenting with confusion and stupor. Although the patient reported was able to initiate a release of ADH, his thirst mechanism was nonfunctional. Only when the patient was compelled to drink water at regular intervals did his serum sodium fall. Robertson and others have described similar cases with abnormalities of thirst causing a type of “central” or “essential” hypernatremia.
Disorders of Sexual Development Related to Hypothalamic Dysfunction (See Also Chap. 27)
This term refers to the abnormally early onset of androgen secretion and spermatogenesis in boys and of cyclic estrogen secretion, and sometimes ovulation, in girls. It is associated with the premature development of secondary sexual characteristics. The occurrence of precocious puberty should prompt both neurologic and endocrine investigations. In the male, one searches for evidence of a teratoma of the pineal gland or mediastinum or an androgenic tumor of the testes or adrenals. In the female with early development of secondary sexual characteristics and menstruation, one seeks other evidence of hypothalamic disease or an estrogen-secreting ovarian tumor.
A hamartoma of the hypothalamus is a leading cause of precocious puberty in both boys and girls. These lesions can be associated with Neurofibromatosis type 1 (von Recklinghausen disease) or the polyostotic fibrous dysplasia of McCune-Albright syndrome). The clinical presentation of these lesions can include so-called gelastic seizures, with involuntary fits of laughing (Breningstall, see “Complex Partial Seizures” in Chap. 15).
Failure of Puberty