Georg Benker

TSH secretion in Cushing's syndrome: relation to glucocorticoid excess, diabetes, goitre, and the sick euthyroid syndrome

Thyrotrophin (TSH) secretion was studied in 63 patients with Cushings syndrome (53 patients with pituitary dependent Cushings disease, eight with adrenocortical tumours, and two with the ectopic ACTH syndrome). Prior to treatment, TSH response to 200 μg of TRH intravenously was significantly decreased compared to controls; TSH response was ‘flat’ (increment < 2 mU/l) in 34 patients (54%). Patients with a flat response to TRH had significantly higher morning and midnight cortisol levels than patients with a TSH response of 2 mU/l and more; this was not due to differences in serum thyroid hormone levels. Basal TSH, TSH increment after TRH, and stimulated TSH value, but not serum triiodothyronine, were correlated with cortisol measurements (0800 h serum cortisol, midnight cortisol, and urinary free corticoid excretion). After exclusion of 40 patients with additional disease (severe systemic disease, diabetes mellitus, or goitre), cortisol ‐ TSH correlations were even more pronounced (r = ‐0.73 for midnight cortisol and stimulated TSH levels), while in the patients with additional complications, these correlations were slight or absent. Successful treatment in 20 patients was associated with a rise in thyroid hormone levels and the TSH response to TRH. These results indicate that (1) the corticoid excess but not serum T3 is the principal factor regulating TSH secretion in Cushings syndrome, (2) a totally flat response to TRH is rare, and (3) TSH suppression and lower than normal serum thyroid hormone levels are reversible after treatment. Since factors like severe systemic disease, diabetes mellitus and goitre also affect TSH secretion, they tend to obscure the statistically significant correlations between cortisol excess and TSH secretion.

Control of prolactin‐secreting macroadenomas with parenteral, long‐acting bromocriptine in 30 patients treated for up to 3 years

OBJECTIVE We investigated the effect of intramuscular injections of long‐acting bromocriptine in patients with macroadenomas.

PHARMACOKINETICS OF ALDOSTERONE IN PATIENTS WITH ADDISON'S DISEASE: EFFECT OF RIFAMPICIN TREATMENT ON GLUCOCORTICOID AND MINERALOCORTICOID METABOLISM

Treatment of tuberculosis with rifampicin in patients with pre‐existing adrenal failure has been reported to induce adrenal crisis due to alteration of Cortisol metabolism by induction of hepatic mixed liver oxygenase enzymes. To determine whether mineralocorticoid metabolism is altered by rifampicin treatment, we established the pharmacokinetics of immunoreactive aldosterone. The metabolic clearance rate (MCR) and plasma half‐life of this material were measured before and after 6 days of rifampicin treatment (600 mg/day) in seven patients with Addisons disease due to tuberculosis. Antipyrine clearance and urinary 6‐β‐hydroxycortisol excretion was determined to demonstrate induction of the cytochrome P 450 dependent enzymes. Infusion of aldosterone at a constant rate of 0‐17 mg/h over 4‐5 h produced steady state concentrations after 2 h, with no difference before and after rifampicin treatment (mean ± SD, 1649 ± 144 vs 1586 ± 80 pg/ml, respectively). The disappearance curve of IR‐aldosterone from plasma was biexponential. No change could be observed in the plasma half‐lives (α‐phase 29 ± 1.9 min vs 30 ± 1.5 min, β‐phase 129 ± 3.2 minra126 ± 4.3min), the MCR (1‐47 ± 0.1 1/h/kg vs 1.46 ± 0.1 1/h/kg vs), and the volume of distribution (9.9 ± 1.9 vs 10.2 ± 0.3 1). The antipyrine half‐life decreased significantly from 12.2 ± 2.6 h to 7.6 ± 0.9 h (P± 0.05) with a rise in antipyrine clearance from 0.38 ± 0.07 to 0.80 ± 0‐23 ml/min/kg (Plt;0.05) and no change in the volume of distribution. Urinary excretion of 6‐β‐hydroxycortisol increased from 711 ± 130 μg/24 h before to 1670 ± 387/μg/24 h (P < 0‐05) after 6 days of rifampicin treatment with no changes in urinary free Cortisol excretion.

BASAL GANGLIA CALCIFICATION IN PSEUDOHYPOPARATHYROIDISM TYPE II

The case history of a patient with basal ganglia calcifications found by computerised tomography is presented. Calcium and phosphorus metabolism showed a pattern suggesting lack of parathyroid hormone (PTH). Further studies revealed increased endogenous PTH levels and urinary cAMP excretion. However, endogenous and exogenous PTH could not elicit the cAMP‐mediated phosphaturic response, indicating pseudohypoparathyroidism type II. The responses of prolactin to TRH and chlorpromazine was impaired. Basal ganglia calcification in pseudohypoparathyroidism type II may represent the only somatic abnormality in this disease apart from the biochemical abnormalities.

CONTINUOUS INFUSION OF GROWTH HORMONE RELEASING HORMONE DOES NOT ALTER THE GROWTH HORMONE RESPONSE TO DIFFERENT STRESS STIMULI

Continuous infusion of GHRH, as well as a bolus injection of GHRH, specifically stimulates the release of GH by the anterior pituitary. However, repetitive bolus injections of GHRH result in diminished responses of GH, while a constant infusion of GHRH cannot maintain high serum GH levels. To investigate whether different GH‐releasing stimuli are able further to challenge the somatotroph being exposed to continuous infusion of GHRH, we determined the GH response to insulin‐induced hypoglycaemia and bicycle exercise. Six normal volunteers received a bolus of 50 μg GHRH or vehicle followed by a continuous infusions of GHRH 1–29 amide (lμg/kg/h) or vehicle for 2.5 h. GHRH bolus and infusion resulted in elevated GH levels, but GH levels fell to values not significantly different from baseline levels after 150 min, GH plasma levels rose again, however, in response to insulin hypoglycaemia and bicycle exercise after both GHRH or vehicle infusion. Thus, the somatotrophs responsiveness to GHRH remains intact to respond to stress stimuli after continuous GHRH infusion.

Hypophosphatämische Osteomalazie@@@Hypophosphatemic Osteomalacia

ZusammenfassungEine erstmals im Erwachsenenalter diagnostizierte hypophosphatämische Osteomalazie ist eine seltene Entität. Sie ist durch ein erniedrigtes Serumphosphat, renalen Phosphatverlust, eine hohe alkalische Phosphatase und eine Osteomalazie charakterisiert. Präsentiert werden der Fall eines Patienten mit typischer Konstellation einer onkogenen (tumorinduzierten) Osteomalazie, die diagnostischen Möglichkeiten und die komplette Heilung nach Entfernung des Tumors. Die neuen Erkenntnisse über die hereditäre und erworbene hypophosphatämische Osteomalazie werden diskutiert.AbstractHypophosphatemic osteomalacia first presenting in adulthood is a rare disease. It is characterized by decreased serum phosphate, renal phosphate wasting, elevated alkaline phosphatase, and osteomalacia. The authors present a case with typical constellation of an oncogenic (tumor-induced) osteomalacia, the possible differential diagnosis, diagnostic evaluation, and complete healing after tumor resection. The new concepts of hereditary and acquired hypophosphatemic osteomalacia are discussed helping us understand this rare disease.