Functional Characterization of Hypothalamic Hyperprolactinemia*

Abstract

PRL secretory dynamics were evaluated by several stimulation and suppression tests in nine patients with hyperprolactinemia due to organic hypothalamic disease. Basal PRL levels ranged between 20-63 ng/ml. There was a normal PRL response to TRH in eight cases (i.e. doubling of basal levels), whereas none of the seven tested subjects responded to sulpiride. The same dissociation of responses was not observed in any of the patients who were still hyperprolactinemic after surgery. Concomitant dopamine infusion resulted in sulpiride-induced PRL release in the four subjects so studied. None of 50 other hyperprolactinemic patients (11 with macroprolactinoma, 18 with microprolactinoma, and 21 with idiopathic hyperprolactinemia) showed PRL response to TRH but not to sulpiride. The TRH-induced PRL increase was significantly higher than that induced by sulpiride in hypothalamic hyperprolactinemia and significantly lower in idiopathic disease as well as in healthy controls; no differences were found in prolactinoma patients. The administration of substances resulting in stimulation of pituitary dopamine receptors, such as dopamine and L-dopa, induced a normal PRL suppression in 7 patients with hypothalamic disease so tested, whereas central nervous system-acting dopaminergic drugs, such as carbidopa plus L-dopa and nomifensine, failed to lower PRL levels in most cases (even when normoprolactinemic after surgery). These data suggest that the mild to moderate hyperprolactinemia found in many patients with hypothalamic lesions is due to dopamine deficiency at the pituitary level, that TRH and dopamine receptors at the lactotropes are intact in this condition, and that paired TRH and sulpiride tests may be of some diagnostic utility in hyperprolactinemic patients. They further suggest that subjects with so-called idiopathic hyperprolactinemia do not suffer from the type of hypothalamic derangement exhibited by patients with organic lesions of the hypothalamus.

Hypothalamic - Pituitary Function in Patients with Idiopathic Growth Hormone Deficiency

“…Increased basal PRL levels are consistent with hypothalamic lesions (36)(37)(38)(39). PRL levels in our patients were however, significantly lower than those found in patients with prolactinomas (40) Both PRL and TSH secretion are inhibited by dopamine (41)(42)(43)(44).…”

“…This decreased PRL response to TRH was previously described in patients with hyperprolactinemia of various etiologies including hypothalamic disease (37,45,46) and was inversely related to basal PRL levels. In 47 patients with GH deficiency and basal PRL levels up to 50 ng/ml we found an inverse correlation between basal PRL and its percent increment after TRH stimulation (r = 0.46, ρ < 0.001).…”

Prolactin Response to the Dopamine Antagonists Sulpiride and Domperidone

“…Since the PRL response to drugs such as sulpiride and domperidone depends on the presence of an inherent dopaminergic tone at the receptor level, as suggested by in vivo studies mentioned in the intro duction as well as by in vitro studies [MacLeod and Robyn, 1977], dynamic testing of PRL secretion with these drugs is of pathophysiological interest as a clinical tool to evaluate the prevalence of dopamine deficiency at the lactotrophs in different hyperprolactinemic states. Thus, the present inves tigation performed in sufficiently large numbers of subjects with the more common causes of hyperprolactinemia suggests that pituitary dopamine deficiency exists in almost all patients with PRL-secreting pituitary mi croadenomas or macroadenomas and with acromegaly and in all subjects with hypothalamic diseases, either organic as previously reported [Ferrari et al, 1982], or 'functional', i.e. subjects with hypopituitarism of hypotha lamic origin [Woolf e t al., 1974], and no evidence of pituitary or suprasellar lesions.…”

“…The failure of dopamine antagonists, including chlorpromazine, metoclopramide, sulpiride and domperidone, to stimulate PRL release in many patients with hyperprolactinemia, and in particular in most of those with prolactinoma, is well known [Kleinberg et al, 1977;Crosignani et al, 1980b;Camanni et al, 1980;Massara et al, 1980], We have previously shown that hyperprolactinemic subjects with either idiopathic disease, microprolactinoma or hypothalamic lesions unresponsive to sulpiride show a clear PRL response to this stimulus during concomitant intravenous infu sion of dopamine [Crosignani et al, 1977;Ferrari et al, 1979Ferrari et al, , 1982, Since dopamine antagonists are known to stimulate PRL release only in the pres ence of dopamine, and since this amine does not cross the blood-brain barrier, we have suggested that restoration of PRL response to sulpiride by dopamine infusion indicates defective dopamine concentration outside the central nervous system (e.g., the pituitary' gland and the median eminence) in tested patients.…”

Normal Lactotroph Sensitivity to Graded Low-Dose Dopamine Infusions in Pathological Hyperprolactinemia

“…A third group of subjects, patients with nonfunctioning pituitary tumors (NFTs) but having hyperprolactinemia as a result of damage to the pituitary stalk or hypothalamus, was also studied. This type of hy perprolactinemia is thought to be secondary to reduced DA delivery [10,30], and, therefore, this group of patients with NFTs is a good model of DA deficiency.…”