Detection of familial dysalbuminaemic hyperthyroxinaemia.

A simple test of in vitro thyroxine binding to serum proteins was used to screen serum samples from euthyroid patients with unexplained increases in the free thyroxine index. A diagnosis of familial dysalbuminaemic hyperthyroxinaemia was presumed in 14 unrelated subjects and six first degree relatives. Increased binding of thyroxine to thyroxine binding prealbumin was diagnosed in one woman with four unaffected relatives. Seven patients with familial dysalbuminaemic hyperthyroxinaemia had been treated for presumed thyrotoxicosis: two had typical Graves' disease and one subacute thyroiditis. Four other patients had been mistakenly treated with radioactive iodine or antithyroid drugs. In previously treated patients familial dysalbuminaemic hyperthyroxinaemia was suspected from the combination of a high serum thyroid stimulating hormone concentration and a normal but invalid free thyroxine index. Physicians should be cautious in accepting a diagnosis of thyrotoxicosis based mainly on a raised serum thyroxine concentration.

Insulin resistance with acanthosis nigricans and acral hypertrophy.

Two patients are described with obesity, acanthosis nigricans, acral hypertrophy, basal hyperinsulinism and exaggerated insulin responses to oral glucose. One patient, a diabetic female showed features of virilisation due to polycystic ovarian disease and underwent gonadectomy with some resolution of her androgenisation and acanthosis nigricans. Binding of labelled insulin to erythrocytes was significantly decreased in both patients compared with normal or obese control subjects. In contrast, the receptor concentration in adipose tissue obtained from the patient undergoing gonadectomy was higher than seen in obese control subjects. Thus, somatic growth may be stimulated by insulin in some tissues in these hyperinsulinaemic patients due to relative preservation of receptor numbers.

Clinical and biochemical evaluation of patients with hirsutism.

Patients with moderate to severe hirsutism presenting over an 18-month period to an endocrine clinic were assessed by clinical evaluation and hormone measurements. Hair growth rate was estimated by a photographic technique and the severity of hirsutism graded using an objective scale. Of 43 patients, 9 had polycystic ovaries and the remainder were considered to have idiopathic hirsutism. The most severely affected group had significantly increased hair growth rates compared with less clinically affected subjects, and 47% of this group showed objective features of virilization. However, apart from a significantly higher 24-hr urine 17-ketosteroid excretion all other hormonal patterns were not significantly different between severely and mildly affected patients. Serum levels of testosterone (T), sex hormone-binding globulin (SHBG), free T (calculated from T and SHBG values), and androstenedione (A) were abnormal in 44%, 51%, 60% and 60% of patients respectively, whereas plasma levels of the specific adrenal androgen DHAS were increased in 40% of patients. There was an overlap between patients with elevated hormone levels, although isolated elevation of T, A or DHAS were seen in 9%, 19% and 3% of patients respectively. In 19% of patients all serum androgen measurements were normal. Gonadotrophin levels were significantly lower in the more severely affected group. Thus androgen levels in patients with idiopathic hirsutism or polycystic ovaries, show considerable overlap with measurements in normal subjects, and elevated plasma androgens may be of adrenal (DHAS) or combined adrenal/ovarian (T, A) origin.

Investigation and treatment of renal calculi associated with hypercalciuria.

Thirty-four patients presenting to a urology clinic over a five-year period with renal calculi and either hypercalciuria or hypercalcemia were investigated by measurements of serum parathyroid hormone and urinary calcium and cAMP. Ten patients were hypercalcemic and were found to have primary hyperparathyroidism. Of the remaining patients all but one had excessive urine calcium excretion after an oral calcium load. In addition, 9 patients were shown to have elevated fasting urinary calcium levels while on a low-calcium diet, raising the possibility of impaired renal calcium conservation as one factor causing their hypercalciuria. The measurement of urinary cAMP levels did not contribute to the accuracy of diagnosis and did not permit further subclassification into different types of hypercalciuria. There was a decrease in urinary calcium excretion and a marked reduction in stone-related events in 10 patients with severe renal stone disease during treatment with hypocalciuric agents.

Investigation and management of symptomatic hyperprolactinaemia.

Fifteen patients with infertility and hyperprolactinaemia have been investigated using tests of prolactin and LH secretion, and treated by prolactin suppression. In addition, 4 patients with hyperprolactinaemia not desiring fertility were also investigated. Of the total group, 16 had galactorrhoea and 15 had amenorrhoea. Pituitary tumours were present in 6 patients and 4 had pituitary microadenomas. Prolactin levels measured by both radioimmunoassay and radioreceptor assay were elevated before treatment and fell during therapy with bromoergocryptine (7.5 mg daily). Tests of prolactin release with TRH and chlorpromazine before treatment did not distinguish patients with functional hyperprolactinaemia from those with pituitary tumours. Basal plasma gonadotrophin concentrations were not elevated despite subnormal urinary oestrogen levels. The serum LH response to LRH was normal during hyperprolactinaemia, but LH release in response to oestrogen provocation was impaired in 14 of 17 patients. During prolactin suppression, mean oestrogen excretion rose significantly and the oestrogen provocation test became normal in all except 2 patients. Pregnancy occurred in all of the 15 patients desiring fertility. Abortion has occurred in 4 patients, all of whom are currently pregnant again. Nine pregnancies have reached term, with no complications from pituitary expansion. It appears that during hyperprolactinaemia there are defects in both positive and negative feedback of oestrogen on LH secretion, and that prolactin suppression in such patients is highly effective in restoring fertility.

A surgical approach to primary hyperparathyroidism, 1971-1976.

Forty-two patients with primary hyperparathyroidism were seen in Auckland Hospital between 1971-1976. These patients were reviewed as to age, sex, mode of presentation, pathology and location of lesions. All were treated surgically. There were two deaths due to severe hypercalcaemia. The value of parathyroid hormone assay and neck vein catheterisation is assessed. The practical aspects of neck exploration for hyperparathyroidism are outlined. The two problems of the treatment of chemical hyperparathyroidism and the recognition and treatment of parathyroid hyperplasia are discussed.

Bromoergocryptin treatment of acromegaly persisting following conventional therapy.

Bromoergocryptine has been used to lower growth hormone concentrations in ten patients with acromegaly in whom previous attempts at pituitary ablation had failed to cure the disorder. Plasma immunoreactive and plasma receptor-reactive growth hormone concentrations together with plasma somatomedin concentrations and urinary excretion of immunoreactive growth hormone were used to assess the response to treatment. Casual immunoreactive hormone concentrations in plasma were lowered to less than 8 mu/l and to less than 5 mu/l during glucose infusion in seven patients, and urinary growth hormone excretion was also brought into the normal range (less than 40 micromicron/12 h) in this group. There was at least a 40% reduction in these measurements in the remaining three patients who had the highest basal hormone concentrations of the group. Plasma somatomedin fell with treatment in eight patients, and intravenous glucose tolerance improved in seven of eight patients tested. Used in modest dosage (up to 15 mg/day) bromoergocryptine can lower plasma and urinary growth hormone and plasma somatomedin concentrations in acromegalic patients in whom previous treatments had decreased but not cured hormone overproduction.

Adaptive enhancement of amino acid transport in human leukemia leukocytes: studies with alpha-aminoisobutyric acid.

Initial rates of accumulation (Vi) of [3-14C] alpha-aminoisobutyric acid (AIB) by human leukemic leukocytes increased markedly and progressively during 240 minute incubations in amino acid-deficient media. Absolute increments were greater in blast cells from patients with acute lymphoblastic leukemia and with acute myeloblastic leukemia than in lymphocytes from patients with chronic lymphocytic leukemia, but per cent increments did not differ. Time-related increases appear to be restricted to an active mechanism for AIB entry and could not be attributed to cell damage, concomitant alterations in the incubation media, or progressive reduction in transinhibition of AIB entry. Studies with two cell populations revealed these increases to be associated with an augmented Vmax and a reduction in apparent Km, suggesting enhanced capacity and affinity of the transport system for AIB. Time-related increases failed to develop in two chronic lymphocytic leukemia (CLL) lymphocyte populations and were partially reduced in two leukemic blast cell populations during continuous exposure to high extracellular AIB concentrations. Hence, this phenomenon may represent an adaptive response to environmental amino acid deprivation. Adaptation may involve de novo protein and RNA synthesis, since it was not seen in cells which were treated with cycloheximide or actinomycin D. However, unlike previous observations in nonmalignant cells, once triggered, the adaptive response was not completely suppressed in leukemic cells which underwent a large degree of adaptation.