J. M. W. Kirk

Gonadal function and response to human chorionic and menopausal gonadotrophin therapy in male patients with idiopathic hypogonadotrophic hypogonadism

OBJECTIVE This study was designed to determine the response to therapy using human chorionic gonadotrophin (hCG) and human menopausal gonadotrophin (hMG) in males with idiopathic isolated hypogonadotrophic hypogonadism (IHH), and to compare the responses in patients presenting with and without cryptorchidism.

Acceleration of pubertal development following pituitary radiotherapy for Cushing's disease

A 7-year-old boy with pituitary dependent Cushings disease was treated with pituitary irradiation following unsuccessful microadenomectomy. This led to normalization of the hypercortisolaemia, but was followed by GH deficiency. Two years after radiotherapy he had the onset of pubertal development with testicular enlargement to 8 ml bilaterally. Pubertal regression was induced using the long-acting GnRH analogue goserelin. Acceleration of skeletal maturation was also arrested, resulting in improvement of final height prediction. Irradiation directly to the hypothalamo-pituitary region, as well as whole brain irradiation, may thus be associated with accelerated pubertal development.

Treatment with GHRH(1-29)NH2 in children with idiopathic short stature induces a sustained increase in growth velocity

OBJECTIVE Therapy with GHRH in patients with mild GH insufficiency appears to be more effective than in those with severe insufficiency. We, therefore, studied the clinical response of children with idiopathic short stature to treatment with GHRH(1‐29)NH2 (GHRHa) for a period of 12 months.

Identification of olfactory dysfunction in carriers of X-linked Kallmann's syndrome

OBJECTIVE The aim of the study was to test the hypothesis that clinically unaffected female carriers of X‐linked Kallmanns syndrome have an olfactory defect.

Growth hormone response to overnight growth hormone-releasing hormone infusion and oral pyridostigmine in children with short stature.

Ross, R.J.M., Savage, M.O., Kirk, J.M.W. and Besser, G.M. (Departments of Endocrinology and Child Health, St Bartholomews Hospital, London, UK). Growth hormone response to overnight growth hormone‐releasing hormone infusion and oral pyridostigmine in children with short stature. Acta Paediatr Scand [Suppl] 349: 114, 1989.

The effects on anterior pituitary hormone secretion of salmon calcitonin in healthy volunteers.

The reports of the effect of calcitonin on pituitary function are confusing and often refer to uncontrolled studies. We have now carried out a double‐blind placebo‐controlled trial of Intravenous and subcutaneous salmon calcitonin on anterior pituitary function in 17 healthy volunteers. Visual analogue scores for the nausea and vomiting seen after salmon calcitonin correlated with the rise in ACTH and, secondarily, Cortisol. Calcitonin had no effect on growth hormone, prolactin, thyrotrophin, luteinizing hormone or follicle stimulating hormone. It is concluded that the stimulation of ACTH secretion following a single dose of salmon calcitonin Is probably the result of the stress of nausea rather than a direct effect on the pituitary.

SUBCUTANEOUS GROWTH HORMONE‐RELEASING HORMONE AUGMENTS PULSATILE NOCTURNAL GH RELEASE IN GH‐INSUFFICIENT CHILDREN, BUT MAY ALSO RAISE BASAL GH SECRETION

Growth hormone‐releasing hormone (GHRH) when given s. c. to GH‐insufficient children either as pulses, or once or twice daily, promotes linear growth. These treatment regimens, however, are not ideal as they require frequent drug administration and a significant proportion of patients do not show improved growth. We have now investigated the GH response to a nocturnal s. c. infusion of GHRH(1–29)NH2, at two dosages, 5 and 10 μg/kg/h, in a group of five GH‐insufficient children. The s. c. infusion of GHRH between 2100 h and 0600 h augmented nocturnal pulsatile GH release in all five children. There was a dose‐dependent response for the GH area under the curve (AUC), and mean total GH concentration. The AUC for GH was significantly greater after the 10 than 5 μg/kg/h GHRH which in turn was greater than that after placebo; mean (SD) AUC: 14816 (3978), 8125 (1931), 3032 (1582) mU min/1 respectively (P < 0.01 and P < 0.05). There was no significant change in the number of GH pulses during the 9‐h infusions when the subjects were infused with GHRH 10 or 5 pg/kg/h compared to placebo, and they occurred at similar times although the number of pulses tended to be greater after GHRH; the mean (SD) numbers of GH pulses were 5.0 (0‐7), 3.8 (0.8), 3.2 (0.8), respectively. There was however a significant rise in the mean baseline GH concentration in all patients during the infusion of GHRH 10 or 5 μg/kg/h compared to placebo, but not with 5 μg/kg/h. Thus, GHRH(1–29)NH2 given s. c. augmented nocturnal pulsatile GH release in GH‐insufficient children but it also increased baseline GH secretion. These results suggest that a sustained release preparation of GHRH could be a potential treatment for GH‐insufficient children, and that a dose of 5 μg/kg/h would promote pulsatile GH release, but that at higher dosage it may also raise basal GH secretion.

Quantitative growth hormone secretion and final adult height

The relationship of quantitative GH secretion to height, growth velocity and puberty is complex and has been the subject of extensive study in children. This study was designed to relate quantitative GH secretion to final height.

Surgical Reinforcement of Gender Identity in Adolescent Intersex Patients

The presentation of phenotypic gender ambiguity at the time of adolescence is uncommon. Surgical reinforcement of gender, or reassignment is often complex and multistage. We present 2 cases of children who developed secondary sexual characteristics contrary to their chromosome status who, because of their late presentation, required significant surgical intervention to reinforce the gender assigned to them. We review some of the surgical techniques involved.

Pyridostigmine fails to increase either spontaneous or GHRH‐stimulated GH secretion during day or night in growth hormone‐insufficient children

objective The aim of the study was to Investigate whether pyridostigmine, a cholinesterase Inhibitor which is thought to act at the hypothalamus to Inhibit somatostatin secretion, would augment spontaneous or GHRH‐stimulated serum GH levels In patients with GH‐insufficiency. DESIGN Oral pyridostigmine 60 mg or placebo was administered at the start of a 9‐h subcutaneous infusion of either GHRH (1–29)NH2 10 μg/kg/h or saline control. Studies were performed during the daytime (0900–1800 h) in five patients, and the night‐time (2100–0600 h) In a further five.