https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(14)61375-1.pdf

Cushing's syndrome

argument is often, if not acrimonious, at least heated. It gives an impression of the fluidity of opinion on many fundamental ideas under discussion and of the urgency with which cardiac cyanosis in the newborn is regarded. When Dr. William Muscott says that the earliest he has operated for pulmonary stenosis is on an infant 3 days old, and Sir Russell Brock agrees that the earlier in the first month that operation is undertaken the better, and when Dr. Varco asks Dr. Senning 'so far as I know they have never yet catheterized any child intrauterine in Sweden, but they have done it through the delivery canal sometimes-would you tell us the indications of the Scandinavian group for catheterization in the immediate newborn period?', one is indeed being kept up with the times. But that was two years ago and already some of the questions then debated have since been answered. This beautifully printed and well-illustrated stiff paperbacked volume is, and will for a few years yet remain, an invaluable companion to a full-scale textbook on congenital heart disease.

Growth at Adolescence.

Objective: The aim was to provide guidelines for evaluation, treatment, and genetic testing for multiple endocrine neoplasia type 1 (MEN1). Participants: The group, which comprised 10 experts, including physicians, surgeons, and geneticists from international centers, received no corporate funding or remuneration. Process: Guidelines were developed by reviews of peer-reviewed publications; a draft was prepared, reviewed, and rigorously revised at several stages; and agreed-upon revisions were incorporated. Conclusions: MEN1 is an autosomal dominant disorder that is due to mutations in the tumor suppressor gene MEN1, which encodes a 610-amino acid protein, menin. Thus, the finding of MEN1 in a patient has important implications for family members because first-degree relatives have a 50% risk of developing the disease and can often be identified by MEN1 mutational analysis. MEN1 is characterized by the occurrence of parathyroid, pancreatic islet, and anterior pituitary tumors. Some patients may also develo...

/pdf/clinical-practice-guidelines-for-multiple-endocrine-iebfm32j0y.pdf

Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1)

Growth hormone treatment can provide benefits in body composition, bone, and quality of life in adults with confirmed growth hormone deficiency.

/pdf/evaluation-and-treatment-of-adult-growth-hormone-deficiency-glkv6ybrr2.pdf

Evaluation and Treatment of Adult Growth Hormone Deficiency: An Endocrine Society Clinical Practice Guideline

Background: Previous guidelines for the management of thyroid nodules and cancers were geared toward adults. Compared with thyroid neoplasms in adults, however, those in the pediatric population ex...

/pdf/management-guidelines-for-children-with-thyroid-nodules-and-1aqe86ijrc.pdf

Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer

The development of anterior pituitary hormone deficiencies has been studied in a group of 165 patients who underwent external radiotherapy for tumours of the pituitary or closely related anatomical sites, and who have been observed for up to 10 years. One hundred and forty had undergone pituitary surgery before radiotherapy. All patients received external radiotherapy by a three-field technique, giving 3750-4250 cGy in 15 or 16 fractions over 20-22 days. A combined test of anterior pituitary function using insulin hypoglycaemia or glucagon stimulation in conjunction with thyrotrophin and gonadotrophin releasing hormone tests and basal estimations of prolactin, thyroid hormones and testosterone or oestradiol was performed before radiotherapy. This was repeated six and 12 months later and subsequently annually. Before radiotherapy, 18 per cent of patients had normal growth hormone secretion, 21 per cent had normal gonadotrophin secretion, 57 per cent had normal corticotrophin reserve and 80 per cent had normal thyrotrophin secretion. Life table analysis demonstrated increasing incidences of all anterior pituitary hormone deficiencies with time: by five years all patients were growth hormone deficient, 91 per cent were gonadotrophin deficient, 77 per cent were corticotrophin deficient and 42 per cent were thyrotrophin deficient. At eight years, respective incidences of deficiencies were 100, 96, 84 and 49 per cent. Radiation-induced hyperprolactinaemia was seen in 73 patients; mean serum prolactin concentration rose from 227 +/- 11 mU/l to a peak of 369 +/- 60 mU/l at two years and subsequently declined towards the basal value. The primary diagnosis, patient age, sex, irradiated tissue volume and previous surgery were examined as variables that might influence the rate of development of anterior pituitary hormone deficiencies, but none of these factors had a significant effect. The radiation induced hyperprolactinaemia was however more marked in female patients. Although anterior pituitary hormone deficiencies most commonly developed in the order growth hormone, gonadotrophin, corticotrophin, thyrotrophin (61 per cent of patients), other sequences were evident. Most notably corticotrophin deficiency occurred before gonadotrophin deficiency. There is a high incidence of anterior pituitary hormone deficiencies in patients treated surgically for pituitary tumours and the incidence increases after external radiotherapy. Deficiencies may occur in an unpredictable sequence and endocrine testing is recommended on an annual basis.

Hypopituitarism following external radiotherapy for pituitary tumours in adults.

Twenty-four patients (three male) with Cushing's disease, aged between 11 and 67 years, were treated with low-dose external pituitary irradiation (20 Gy in eight fractions over 10-12 days) and followed for between 13 and 171 months (median 93 months). Eleven patients (46%) went into remission 4-36 months after irradiation, but five subsequently relapsed. Two of these received no further active treatment, one underwent successful pituitary surgery, one underwent a second course of low-dose external irradiation (as yet unsuccessful) and one has been treated with metyrapone for a total of 75 months. One of the 13 patients who did not respond received a further course of low-dose pituitary irradiation with prompt remission and two have received metyrapone for 41 months and 15 years without ill effect. One patient died from cerebrovascular disease. The remaining nine patients underwent bilateral adrenalectomy (one after unsuccessful pituitary surgery) with rapid resolution of hypercortisolism. Five of these patients have developed hyperpigmentation and elevated ACTH levels (range 505-1150 ng/l). A pituitary microadenoma has been demonstrated on CT scan in three and successfully removed by microadenomectomy. In the present series, the low incidence of radiation-induced hypopituitarism and absence of other complications attributable to radiotherapy suggest that low-dose pituitary irradiation may be a useful treatment option in selected patients. However, long-term follow-up has demonstrated a high relapse rate and failure to prevent Nelson's syndrome in adrenalectomized patients, indicating that it should not be used as primary treatment in preference to selective adenomectomy.

Long-term follow-up of low-dose external pituitary irradiation for Cushing's disease.

. Growth hormone (GH) secretion has been studied under physiological conditions and in response to standard pharmacological stimuli in 14 children, who had previously received cranial irradiation between two and fourteen years earlier. All fourteen showed a blunted GH response to insulin hypoglycaemia and, in twelve, the GH response to arginine stimulation was also subnormal. Physiological GH secretion was studied by measuring integrated GH concentrations in 30 min blood samples collected over a 24 hour period by a continuous withdrawal pump. Compared to normal controls (n=5), the irradiated patients showed a significant reduction in the mean integrated GH concentration (2.2: 8.8 mU/l; p< 0.002), the total 24 hour GH output (mean 105.7 mU vs. 391.7 mU; p< 0.002) and the mean GH output during the first six hours of sleep (mean 48.2 mU vs. 226 mU; p< 0.002). There was no significant correlation between the maximum peak GH response to either pharmacological test and the total 24 hour GH output. Conventionally most short children undergo two provocative tests of GH release and if the GH response to one of the two tests is normal, it is usually assumed that GH production is adequate. Adopting these criteria in this study it would have been assumed incorrectly that GH production was normal in two children. Nonetheless all 14 children showed a blunted GH response to an ITT as well as a reduced total 24 hour GH output. Therefore we would suggest that in children suspected of radiation-induced GH deficiency pharmacological tests of GH secretion remain useful, the ITT being the test of choice because of the marked radiation sensitivity of the GH response to hypoglycaemia.

The effects of cranial irradiation on growth hormone secretion.

Nineteen patients with Cushing's disease were treated with low dose external pituitary irradiation (20 Gy (2000 rad) in eight fractions over 10 days). While awaiting the effects of pituitary irradiation all patients were treated with metyrapone. Seven patients had a complete remission of their disease within six to 12 months of irradiation. They did not require any further treatment and were followed up for a mean of three and a half (range one to eight) years. Another patient had a complete remission after a second course of pituitary irradiation. A further two patients showed a significant biochemical improvement after irradiation, although they were not rendered eucorticoid. There were no complications after this dose of irradiation. These results compare favourably with those reported after pituitary irradiation at conventional doses (40-50 Gy (4000-5000 rad) over four or five weeks) but were not associated with any complications. It is therefore recommended that low dose external pituitary irradiation be used as definitive first line treatment for Cushing's disease.

S. R. Ahmed

Papers

Hypopituitarism following external radiotherapy for pituitary tumours in adults.

Long-term follow-up of low-dose external pituitary irradiation for Cushing's disease.

The effects of cranial irradiation on growth hormone secretion.

Treatment of Cushing's disease with low dose radiation therapy.

Treatment of Cushing’s Disease With Low Dose Radiation Therapy