Hyperprolactinaemia is associated with a higher prevalence of pituitary-adrenal dysfunction in non-functioning pituitary macroadenoma.

In non-functioning pituitary macroadenoma (NFMA), hyperprolactinaemia (hyperPRL) is considered to be a sign of hypothalamic-pituitary dysregulation, but it is unknown whether hyperPRL is associated with an increased frequency of pituitary hormone deficiencies. Forty consecutive patients with histology-proven NFMA were studied and hyperPRL was defined as serum prolactin (PRL) > 200 mIU/l in men and > 600 mIU/l in women. The pituitary-adrenal axis was evaluated by measurement of urinary free cortisol (N = 38), peak cortisol to insulin-induced hypoglycaemia (IIH, N = 36) and to human corticotrophin-releasing hormone (hCRF, N = 40) and by urinary tetrahydrol 11-deoxycortisol (H4S, N = 39), plasma androstenedione increment (N = 39) and serum 11-deoxycortisol (N = 1) after metyrapone. Central hypothyroidism, gonadotrophin deficiency and growth hormone (GH) reserve were also assessed. Twenty patients had hyperPRL (serum PRL 331 (223-1120) mIU/l (median, range) in men and 932 (660-3927) mIU/l in women): urinary free cortisol excretion (p < 0.03) and peak serum cortisol in response to IIH (p < 0.02) were lower in hyperPRL than in normoPRL patients; peak serum cortisol after hCRF was not different between groups but occurred later in hyperPRL patients (at 60vs 30 min, p < 0.03); urinary H4S excretion and androstenedione response after metyrapone were lower in hyperPRL than in normoPRL patients (p < 0.05 for both): 60% of hyperPRL patients and 15% of normoPRL patients had an abnormal H4S response (p < 0.025): central hypothyroidism (overt + subclinical) was present in 74% of hyperPRL and in 60% of normoPRL patients (NS); 78% of hyperPRL and 55% of normoPRL patients had gonadotrophin deficiency (NS): growth hormone (GH) deficiency was present in 83% of hyperPRL and in 89% of normoPRL patients (NS); 73.3% of 75 evaluable pituitary hormone axes were abnormal in hyperPRL patients compared to 53.8% of 78 hormone axes in normoPRL patients (by metyrapone test to examine adrenal function, p < 0.025); and no significant differences in tumour grade and stage distribution were found between hyperPRL and normoPRL patients. It is concluded that hyper-prolactinaemia in NFMA is associated with a higher prevalence of pituitary-adrenal dysfunction, which is likely to be explained at least in part by functional hypothalamic-pituitary interruption.

The assessment of the functional capacity of the hypothalamic-pituitary-adrenal axis by measurement of basal plasma and urinary cortisol in comparison with insulin-induced hypoglycaemia and metyrapone tests.

In 58 patients with a pituitary adenoma or hypothalamic-pituitary disease an insulin-induced hypoglycaemia test and a metyrapone test were performed. The results of these tests were compared with morning plasma cortisol levels and daily urinary cortisol excretion as indicators of insufficiency of the pituitary-adrenal axis. Basal unstressed urinary cortisol excretion was insufficient in 20 cases. These patients, needing life-long glucocorticoid substitution therapy, were excellently detected by both tests and daily urinary cortisol excretion. The predictive value of the morning plasma cortisol level was inferior to these. Five cases with sufficient basal cortisol excretion showed a defective adrenal response to hypoglycaemia. These patients were not discriminated by the metyrapone test, urinary cortisol excretion or plasma cortisol levels. It is concluded that urinary cortisol excretion can safely replace the hypoglycaemia and metyrapone test for the detection of insufficient basal cortisol production in patients with hypothalamic and/or pituitary disorders.

[Comparison of iodine scintigraphy and computerized tomography in the localization of pheochromocytoma]. / Vergelijking van jodium-scintigrafie en computertomografie bij de lokalisatie van het feochromocytoom.

A comparison is made of the results of CT scanning and MIBG scintigraphy in the localization of phaeochromocytoma. In 21 out of 24 patients with clinically diagnosed phaeochromocytoma in the University Medical Hospital, Groningen in 1983-1990, MIBG scintigraphy provided accurate localization, while in 16 out of 18 patients with phaeochromocytoma who underwent CT scanning a correct localization was obtained. False negative results were mainly present when lesions were smaller than 2 cm. There were no false positive results. It is concluded that the sensitivity of the two methods in the localization of phaeochromocytoma is about equal. The use of one of the methods rather than of both is advised.

Paternity in idiopathic hypothalamic hypogonadism during testosterone therapy in two unrelated patients.

When fertility is desired, idiopathic hypothalamic hypogonadism is amenable to treatment with pulsatile low dosage GnRH administration or injections of gonadotrophins. Patients with this disorder are hypogonadal and require therapy with androgens or oestrogens/progestagens. This would presumably lower pituitary gonadotrophin production even further. However, fertility occurring spontaneously during testosterone substitution, as proven by paternity testing, has been described twice. The present report adds two more cases. It is unwise to make a definite statement about infertility in male patients with this condition.

Hypogonadism in untreated male normoprolactinaemic acromegalics.

Hypogonadism is a distinct feature of acromegaly, even in the absence of hyperprolactinaemia. In 10 untreated male acromegalics, aged 24 to 46 yr, without evidence of any other disturbance of anterior pituitary function, low testosterone values were found in the presence of a normal reaction of pituitary gonadotrophins following GnRH administration. In three patients, one injection of 5000 IU hCG resulted in a sharp rise in testosterone. Although we were unable to elicit a similar reaction pattern of the GnRH-gonadotrophins-testosterone axis following administration of biosynthetic methionyl-hGH, it is suggested that suppression of testicular function in untreated acromegaly without other endocrine disturbances may be partly caused by increased somatostatin production.

Incomplete virilization and subclinical mineralocorticoid excess in a boy with partial 17,20-desmolase/17 alpha-hydroxylase deficiency.

A 17-year-old boy is described with impaired virilization and subclinical mineralocorticoid excess owing to combined 17,20-desmolase/17 alpha-hydroxylase deficiency. His basal plasma progesterone was 20.9 nmol/l (reference value 0.50-1.88), 17-hydroxyprogesterone 21.3 nmol/l (reference value 3.05-4.84), testosterone 6.85 nmol/l (reference value 14.1-22.0), and his excretion of tetrahydro-11-deoxycorticosterone 11.8 mumol/24 h (reference value 1.0-1.5). The differential effects of this combined enzyme deficiency on adrenal and testicular function were studied by ACTH stimulation, dexamethasone suppression, hCG stimulation, and suppression treatment with testosterone.

Invasive fibrous thyroiditis (Riedel's struma): a manifestation of multifocal fibrosclerosis? A case report with review of the literature.

A patient is described with Riedel's thyroiditis and invasive fibrous growth in parathyroid, lacrimal glands, and retroperitoneally. It is proposed that Riedel's thyroiditis is not a disease in its own right but a manifestation of a generalized disease of fibrous tissues.

The usefulness of a sensitive thyrotrophin assay in the fine adjustment of thyroxine therapy following ablation for carcinoma.

The usefulness of FT4 and FT3 measurements as an index of adequate thyroxine treatment in differentiated thyroid cancer was evaluated in 25 athyreotic patients on two occasions with an interval of at least 6 months. The determinations were combined with a TRH test. The TSH measurements were performed using a sensitive immunoassay. The great interindividual differences in absorption and metabolism of thyroxine made the measurements of FT4 and FT3 unsuitable for fine adjustment of thyroxine substitution therapy. When all patients are divided into 4 categories according to their TRH test (1: delta TSH less than or equal to 1 mU/l; 2: greater than or equal to 1 less than or equal to 4 mU/l; 3: greater than 4 mU/l and 4: basal TSH greater than or equal to 6 mU/l), there is a considerable overlap between these categories in relation to FT4 and FT3. In the second TRH test all patients were found to belong to the same category when their thyroxine dose had not been changed. A basal TSH level below 0.30 mU/l suggests nearly complete suppression of TSH secretion. However, a TRH test is necessary to allow a definite conclusion to be drawn. It is argued that complete suppression of TSH is not necessarily desirable in patients with treated thyroid carcinoma. From the results of our study it would seem advisable to use the TRH test once to adjust the thyroxine dose in such a manner that subnormal basal TSH is achieved as in the second category. Once the dosage has been established, a determination of basal TSH suffices in follow-up.

The assessment of hypothalamic pituitary maturation during puberty with a combined clomiphene citrate/GnRH test in boys.

The diagnosis of idiopathic delayed pubertal development in boys is difficult. A single GnRH test does not give information concerning hypothalamic maturity. After one week clomiphene citrate administration the LH reaction pattern is enhanced in subjects with maturing and depressed in subjects with immature hypothalamic-pituitary function.

Plasma 11-deoxycortisol, androstenedione, testosterone and ACTH in comparison with the urinary excretion of tetrahydro-11-deoxycortisol as indices of the pituitary-adrenal response to oral metyrapone.

Plasma levels of ACTH, 11-deoxycortisol, androstenedione and testosterone and urinary tetrahydro-11-deoxycortisol were determined during a two day oral metyrapone test using doses of 1.5 g every 6 h. The level of 11-deosycortisol 48 h after the start was distinctive regarding the assessment of pituitary ACTH secretory capacity. The rise of androstenedione concentration after 48 h is distinctive in a similar way, whereas ACTH determination is of little diagnostic value in this respect. Further, an increase in testosterone level can be observed in cases of low basal testosterone production. This increase is probably the result of peripheral conversion of androstenedione to testosterone. Where the basal testosterone concentration was high, no change could be measured.

A gonadotrophin responsive testosterone producing adrenocortical adenoma and high gonadotrophin levels in an elderly woman.

A gonadotrophin response testosterone producing adrenal cortical adenoma in a 61-year-old woman is described. Oophorectomy was performed before adrenalectomy as at first an ovarian origin of excess and androgen production was suspected. The hypophyseal gonadal feedback system was studied after oophorectomy using LHRH before and after administration of ethinyloestradiol. After adenalectomy this study was repeated using ethyinyloestradiol at two dose levels and after premedication with testosterone. In this patient the LH feedback system behaved similarly to that observed in Klinefelter's syndrome and in patients with anorchia.

The effect of short-term testosterone treatment in boys with delayed puberty.

Eight boys with severely delayed puberty without pathological cause were treated for 6 months with testosterone. This resulted in acceleration of skeletal maturation and a marked increase in height and weight. No adverse effects were found on hypothalamic-pituitary and gonadal maturation. Basal LH, FSH and testosterone levels rose to nearly adult values at follow-up within a year and pituitary responsiveness to LH-RH increased markedly.

The effect of LH-RH infusion on serum LH, FSH and testosterone in boys with advanced puberty, delayed puberty and hypogonadotrophic hypogonadism.

LH-RH injection and infusion studies were performed in advanced puberty, delayed puberty and hypogonadotrophic hypogonadism. No differential diagnosis could be made between delayed puberty and hypogonadotrophic hypogonadism using LH-RH injection. In the LH-RH infusion studies evidence was obtained that stimulation of the pituitary during 4 h results in continuously rising LH levels in advanced puberty and in delayed puberty while in hypogonadotrophic hypogonadism the secretory capacity of the pituitary is gradually exhausted. This phenomenon can be used in the differential diagnosis between delayed puberty and hypogonadotrophic hypogonadism. Though the FSH data point in the same direction they are not useful in this connection as the overlap between the different categories was considerable.

[Primary amenorrhoea, hypertension, and hypokalaemia in 17-hydroxylase deficiency, a not uncommon condition (author's transl)]. / Primäre Amenorrhoe und Hypokaliämie infolge 17alpha-Hydroxylase-Mangels.

Five phenotypic female patients with primary amenorrhoea, mild hypertension, and hypokalaemia are described. The condition originates from 17-hydroxylase deficiency in both adrenals and gonads. Two cases had a XY chromosome pattern, two cases were familial. It is suggested to determine serum potassium in all cases with unexplained primary amenorrhoea.

Synthesis of 14C-meglumine salicylate and its disposition in humans after oral administration.

The synthesis of 14C-meglumine salicylate was accomplished by heating 14C-meglumine with salicylic acid, in equimolar ratios, in 2-propanol. The average radiochemical yield was 97.5%. Ten healthy adult male volunteers were given 1.2 g of the compound orally. Five took 1.2 g of 1-deoxy-1-[14C]-methylamino-D-glucitol salicylate (containing about 47 micronCi), and five others took 1.2 g of 1-deoxy-1-methylamino-D-[U-14 micronCi), and five others took 1.2 g of 1-deoxy-1-methylamino-D-[U-14C]-glucitol salicylate (containing about 45 micronCi). Urine and feces were collected for 5 days, and blood was sampled for 24 hr. The peak urinary excretion of meglumine and/or its metabolites occurred between 4 and 8 hr after administration (about 7.2% of the administered dose). Meglumine was excreted primarily in the feces (72.4% over 5 days) and, to a smaller extent, in urine (21.3% over 5 days). No activity was detected in blood. The excretion rate and percentage excreted were the same for both groups of subjects, suggesting that meglumine was not metabolized by N-demethylation or conversion to carbon dioxide. The highest blood salicylate level, 44.4 +/- 1.9 microng/ml, was observed 1 hr after administration. Urinary levels of salicylic acid and its metabolites were observed to be at a maximum at 8 hr. Total salicylate recovery was 94.7 +/- 1.5% in 48 hr. Salicyluric acid was the major metabolite, accounting for 69.5 +/- 3.6% of the dose. Salicylic acid accounted for 6.8 +/- 1.2%.

Differential response of serum LH in hypogonadotropic hypogonadism and delayed puberty to LH-RH stimulation before and after clomiphene citrate administration.

The differential diagnosis between hypogonadotropic hypogonadism and delayed puberty is facilitated by comparing the response of gonadotropins to LH-RH stimulation before and after administration of clomiphene citrate 200 mg daily during 7 days. Premedication of clomiphene citrate depresses peak values of LH and FSH on LH-RH in delayed puberty. In hypogonadotropic hypogonadism clomiphene citrate raises LH-RH induced peak LH while FSH does not change.

Absorption, distribution, and excretion of 14C-meglumine in rats and dogs after administration of 14C-meglumine salicylate.

Meglumine labeled with carbon-14 was administered orally as 14C-meglumine salicylate to rats and dogs to study its distribution and excretion. The compound was incompletely absorbed; that which was absorbed was rapidly excreted in the urine. Peak blood levels were about 5-10 mug/ml in rats and 2-8 mug/ml in dogs. Tissue levels were negligible at the end of the experimental periods. No evidence for N-demethylation or oxidation to carbon dioxide was obtained.