Combined Anterior Pituitary Function Test Research Articles

Mineralocorticoid status and endocrine dysfunction in severe hemochromatosis.

Selective iron deposition in the zona glomerulosa of the adrenal cortex is observed in hemochromatosis. Hypoaldosteronism should be excluded before starting venesection, to avoid long-term volume depletion. We evaluated the aldosterone status in patients with hemochromatosis. As other endocrine organs can be affected by the disease as well, we simultaneously evaluated anterior pituitary, gonadal, thyroid and pancreatic beta-cell activity. Nine patients with hereditary or acquired hemochromatosis and highly increased plasma ferritin levels were investigated. In patients, liver cirrhosis had been confirmed histologically. Five patients complained of sexual dysfunction, and one had impaired glucose tolerance. Plasma aldosterone (PA) and renin activity (PRA) were measured after a period of normal (100 mmol/day) and low (10 mmol/day) sodium intake. A combined anterior pituitary function test and a glucagon stimulation test were undertaken to evaluate other endocrine functions. Both PA and PRA levels were decreased in one patient with liver cirrhosis, who also presented attenuated cortisol, prolactin and gonadotrophin secretion. No patients had signs of primary hypoaldosteronism with hyperreninemia. Hypogonadotropic hypogonadism was observed in 3 males and 1 female. Pituitary ACTH reserve was impaired in 2, GH and prolactin response in 1, and thyroid function in none of the patients. Glucagon-stimulated plasma C-peptide was impaired in one patient. In conclusion, primary aldosterone deficiency was not observed in patients with severe iron overload. Hyporeninemic hypoaldosteronism was found in one patient who also presented other endocrinopathies. Hypogonadotropic hypogonadism is the most frequent endocrine abnormality in hemochromatosis.

Residual pituitary function after transsphenoidal hypophysectomy in dogs with pituitary-dependent hyperadrenocorticism.

Pituitary function was assessed before and after transsphenoidal hypophysectomy in 39 dogs with pituitary-dependent hyperadrenocorticism (PDH). Anterior pituitary function was investigated using combined administration of four hypophysiotropic releasing hormones (corticotropin-releasing hormone (CRH), GHRH, GnRH, and TRH) with measurements of ACTH, cortisol, GH, LH, prolactin (PRL), and TSH Pars intermedia function was assessed by measurements of basal plasma alpha-MSH concentrations and adrenocortical function by baseline urinary corticoid/creatinine ratios. At eight weeks after hypophysectomy basal plasma ACTH, cortisol, GH, LH, PRL, and TSH concentrations were significantly lower than before surgery. In seven dogs with elevated alpha-MSH concentrations, the values returned to the normal level after surgery. In the combined anterior pituitary function test there were no plasma GH, LH, PRL, and TSH responses to stimulation, whereas plasma ACTH and cortisol responses were small but significant. Remission of hyperadrenocorticism was obtained in 35 dogs and recurrences occurred in 3 of these within 16 months postoperatively. At 8 weeks after hypophysectomy, these 3 dogs were not discernible, with respect to residual pituitary and adrenocortical function, from the 32 dogs with persisting remission. Urinary corticoid/creatinine ratios in the latter group of dogs did not increase during 22 months after hypophysectomy. In contrast to the presurgical findings, at 8 weeks after hypophysectomy there were significant positive correlations between baseline urinary corticoid/creatinine ratios and basal levels and responses for ACTH, indicating return to normal function of the pituitary-adrenocortical axis. It is concluded that among the adenohypophyseal cells present in the sella turcica after hypophysectomy, the corticotropes have a distinct behavior. Much more so than the other cell types, the unaffected corticotropes tend to remain functional, or a repressed reserve fraction of corticotropes may become functional. This may be due to the removal of the hypothalamic influence of a postulated corticotropin-release inhibiting factor or a diminished inhibitory influence of a postulated paracrine factor. The corticotropes may maintain normocorticism, but may also lead to mild recurrence after relatively long periods of remission.

Transsphenoidal hypophysectomy in beagle dogs: evaluation of a microsurgical technique.

Assessment of a microsurgical technique for transsphenoidal hypophysectomy in dogs. Prospective study using physical examination, pituitary function testing, computed tomography (CT), and histological examination at autopsy. Eight laboratory beagle dogs. Pituitary function was assessed before and at 10 weeks after hypophysectomy by combined administration of four releasing hormones (anterior pituitary), administration of haloperidol (pars intermedia), and infusion of hypertonic saline (posterior pituitary). CT imaging enabled accurate preoperative localization of the pituitary. Appropriate positioning and surgical technique facilitated exposure of the pituitary and its extraction without hemorrhage. Postoperative recovery was generally uncomplicated. None of the eight dogs had somatotropic, gonadotropic, lactotropic, melanotropic, or posterior pituitary responses to stimulation at 10 weeks after hypophysectomy. Four dogs (ACTH nonresponders) also had no corticotropic response and four (ACTH responders) had small but significant responses in the combined anterior pituitary function test. Adrenocortical atrophy was more pronounced in the ACTH nonresponders than in the responders. No residual pituitary tissue was found along the ventral hypothalamic diencephalon but nests of pituitary cells were found embedded in fibrous tissue in the sella turcica. The surgical technique proved to be safe and effective. Microscopic nests of pituitary cells in the sella turcica may be responsible for residual corticotropic response to hypophysiotropic stimulation after hypophysectomy. The surgical technique may be used in the treatment of dogs with pituitary-dependent hyperadrenocorticism. The corticotropic response is the most sensitive criterion in assessing completeness of hypophysectomy in dogs.

Assessment of a combined anterior pituitary function test in beagle dogs: Rapid sequential intravenous administration of four hypothalamic releasing hormones

A combined anterior pituitary (CAP) function test was assessed in eight healthy male beagle dogs. The CAP test consisted of sequential 30-second intravenous administrations of four hypothalamic releasing hormones in the following order and doses: 1 μg of corticotropin-releasing hormone (CRH)/kg, 1 μg of growth hormone-releasing hormone (GHRH)/kg, 10 μg of gonadotropinreleasing hormone (GnRH)/kg, and 10 μg of thyrotropin-releasing hormone (TRH)/kg. Plasma samples were assayed for adrenocorticotropin, cortisol, GH, luteinizing hormone (LH), and prolactin (PRL) at multiple times for 120 min after injection. Each releasing hormone was also administered separately in the same dose to the same eight dogs in order to investigate any interactions between the releasing hormones in the combined function test. Compared with separate administration, the combined administration of these four hypothalamic releasing hormones caused no apparent inhibition or synergism with respect to the responses to CRH, GHRH, and TRH. The combined administration of these four hypothalamic releasing hormones caused a 50% attenuation in LH response compared with the LH response to single GnRH administration. The side effects of the combined test were confined to restlessness and nausea in three dogs, which disappeared within minutes after the administration of the releasing hormones. It is concluded that with the rapid sequential administration of four hypothalamic releasing hormones (CRH, GHRH, GnRH, and TRH), the adenohypophyseal responses are similar to those occurring with the single administration of these secretagogues, with the exception of the LH response, which is lower in the CAP test than after single GnRH administration.

MODIFICATIONS OF THERMOREGULATION IN PATIENTS WITH SUPRASELLAR PITUITARY ADENOMAS

Thermoregulation was investigated pre and postoperatively in 5 and only preoperatively in 7 patients with suprasellar pituitary adenomas by exposing them to external cold and heat in a climatic chamber. Five healthy subjects served as controls. Body core and skin temperatures, oxygen consumption, electromyographic activity, skin blood flow and local sweating rates were continuously measured. Threshold temperatures for activation of heat production and heat loss were calculated from these data. Hormone analysis was performed before and after stimulation with releasing factors. In the patients, core temperatures as well as threshold temperatures for heat production and heat loss were elevated by about 0.5 degrees C as compared with controls. This elevation of core and threshold temperatures was achieved, despite a reduced resting metabolic rate, by a reduction of skin blood flow indicated by a low mean skin temperature. After successful operation the thermoregulatory alterations normalized. Serum levels of growth hormone were reduced preoperatively and stimulation by GHRF did not cause an appropriate increase. Prolactin was elevated in 6 patients with prolactinomas, but there was no correlation with changes in thermoregulatory threshold temperatures. Stimulation of the other hypophyseal hormones by the combined anterior pituitary function test revealed a normal hormonal response. Apart from prolactin there were no significant hormonal changes postoperatively. It is concluded that disturbances of temperature regulation are present in patients with suprasellar adenomas, but that they are not detectable by routine clinical methods. These alterations probably depend on a disturbance of hypothalamic function and are reversible by surgery.

Specific Effect of CV 205-502, a Potent Nonergot Dopamine Agonist, During a Combined Anterior Pituitary Function Test*

CV 205-502, an octahydrobenzo[g]quinoline, is a dopamine agonist compound that is not an ergot or ergoline derivative. To investigate the site of action of CV 205-502, three groups of five men were given single daily doses of CV 205-502 (0.04, 0.06, or 0.08 mg/day, doses that suppress plasma PRL by 60-80% for 24 h) for 5 days; on day 6 a combined anterior pituitary function test using iv administration of four hypothalamic releasing hormones (TRH, 200 micrograms; GHRH, 100 micrograms; CRH, 100 micrograms; LHRH, 100 micrograms) was performed. One month later the challenge tests were repeated to obtain control values. The following hormones were measured by RIA in plasma: TSH, ACTH, cortisol, PRL, GH, LH, FSH, and testosterone. With the exception of plasma PRL levels, basal and releasing hormone-stimulated values were similar after CV 205-502 administration and after the 1-month washout period. Basal plasma PRL was lower after CV 205-502 administration, and the response to TRH was attenuated by all three doses of CV 205-502 (the mean percent inhibition values were 76%, 93%, and 94%, respectively). All three doses of CV 205-502 were well tolerated, and another group of men well tolerated 0.1 mg daily. The results confirm that CV 205-502 is a potent dopamine agonist, which directly inhibits lactotropic cells but has no effect on other pituitary cell types.

The effect of SMS 201-995, a long-acting somatostatin analogue, on anterior pituitary function in healthy male volunteers.

The endocrine effect of SMS 201-995, an octapeptide analogue of somatostatin, was assessed during a combined anterior pituitary function test. There was no effect on the extent of hypoglycaemia after intravenous insulin infusion or on the subsequent rate of recovery of plasma glucose. SMS 201-995 administration, however, resulted in a profound and selective suppression of the GH response to hypoglycaemia without affecting the ACTH or cortisol responses. There was also a marked reduction of TSH release in response to intravenous TRH; the prolactin response was unimpaired. The LH response to LHRH was blunted and the FSH response unaffected. SMS 201-995 does not significantly impair the counterregulatory mechanisms in response to hypoglycaemia, and, in particular, the hypothalamic-pituitary-adrenal axis remains intact.

Rapid sequential intravenous administration of four hypothalamic releasing hormones as a combined anterior pituitary function test in normal subjects.

Normal subjects were studied to test the feasibility of a combined anterior pituitary function test using iv administration of four hypothalamic releasing hormones: ovine corticotropin-releasing hormone, human GH-releasing hormone, GnRH, and TRH. Initially, nine normal men were studied with various combinations of these four hormones to exclude the possibility that they might inhibit or synergize with each other in releasing the individual anterior pituitary hormones. When given in combination, the releasing hormones were administered as sequential 20-sec iv infusions in the following order and doses: ovine corticotropin-releasing hormone, 1 microgram/kg; GnRH, 100 micrograms; human GH-releasing hormone, 1 microgram/kg; and TRH, 200 micrograms. Plasma or serum samples were assayed for ACTH, cortisol, GH, PRL, FSH, LH, and TSH at multiple times for 120 min after injection. Compared to individual administration, combined administration of these four hypothalamic releasing hormones caused no apparent inhibition or synergism with respect to the individual hormone responses of these normal subjects. Side-effects of the combined test were the same as those observed with individual hormone administration. No unusual or dangerous side-effects were observed. Having confirmed the efficacy of combined administration of the four releasing hormones, we administered the combination to five additional normal men and 12 normal women. Anterior pituitary hormone and cortisol responses were the same in men and women, except for a lower LH and a greater PRL response in women. There was a rapid increase in all hormones, with peak levels usually reached by 60 min. Adequate assessment of individual hormone responses can be achieved by assaying a basal and only 2 (or 3 in the case of ACTH and GH) postinfusion samples. A rapid, safe, and useful test of combined anterior pituitary function appears to be feasible using these four hypothalamic releasing hormones.