Subclinical pulmonary haemorrhage causing a restrictive lung defect in three siblings with a unique urticarial vasculitis syndrome.

Three siblings with urticarial vasculitis syndrome (UVS) are described. All had restrictive lung function abnormalities caused by subclinical pulmonary haemorrhage. The latter was suspected after finding haemosiderin-laden macrophages and a friable bronchial mucosa during elective bronchopulmonary alveolar lavage (BAL). The chest radiographs were normal at presentation but after steroid withdrawal symptoms worsened, haemoglobin levels fell, and Case 1 developed acute pulmonary haemorrhage. This was documented by lung biopsy, which also revealed evidence of old haemorrhage and fibrosis. We concluded that these patients had a unique familial variant of UVS with a previously unreported restrictive lung disease due to subclinical pulmonary haemorrhage.

Massive rise in thyroglobulin with adult respiratory distress syndrome after embolisation of thyroid cancer metastasis.

A patient with long-standing metastatic disease from a well differentiated papillary cell carcinoma of the thyroid underwent embolisation of a painful large sacral metastasis. Following embolisation she had a massive rise in circulating serum thyroglobulin (Tg) levels coinciding with the development of adult respiratory distress syndrome (ARDS) on the tenth day without any other obvious cause. The patient subsequently recovered. The time course suggests that ARDS in this case might have resulted from aggregation of Tg molecules in the pulmonary microcirculation.

Ablation of the thyroid remnant and 131I dose in differentiated thyroid cancer.

AIMS: To compare the efficacy of remnant ablation following a single low dose (specific activity of 131I administered, 1074-1110 MBq) vs. a single high dose (mostly 2775-3700 MBq) of 131I in patients with differentiated thyroid cancer and to determine whether or not the extent of surgery influences outcome. METHODS: Nineteen studies have reported the results of low dose 131I ablation. Of these, 11 met our criteria for a comparative analysis. Two additional cohorts of ours were added and these were analysed in two groups based on the extent of surgery (near-total [NT; Woodhouse1] vs. sub-total [ST; Woodhouse2]). There were 518 low dose and 449 high dose patients in all. RESULTS: The average failure of a single low dose was 46 +/- 28% (SD). Meta-analysis revealed a statistically significant advantage for a single high over a single low dose and a pooled reduction in relative risk of failure of the high dose of about 27% (P < 0.01). From this we estimate that for every seven patients treated one more would be ablated given a high rather than a low dose (assuming a low dose failure risk of 50%). Also, a significantly greater proportion of patients are ablated after a single high or low dose, if they underwent near-total as opposed to sub-total thyroidectomy (summary relative risk (RR) 1.4; P < 0.05). CONCLUSION: High dose 131I is more efficient than low dose for remnant ablation particularly after less than total thyroidectomy. Results suggest that patients with differentiated thyroid cancer should routinely have a total thyroidectomy followed by high dose 131I (2775-3700MBq) for ablation of the remnant.

Hypernatremic metabolic myopathy due to hypothalamic dysfunction.

We report a patient with muscle weakness secondary to elevated serum sodium level. The cause of the elevated sodium level and the mechanism involved in producing muscle weakness are discussed.

Acute and long-term effects of octreotide in patients with ACTH-dependent Cushing's syndrome.

PURPOSE: Octreotide is of proven efficacy in the management of patients with acromegaly, thyrotropin-secreting pituitary adenomas, and certain gastrointestinal tumors, but its effect in Cushing's syndrome is less clear. PATIENTS AND METHODS: We studied 10 patients who presented with adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome, 3 of whom were previously adrenalectomized. Serum cortisol or ACTH levels were measured before and during the administration of octreotide 50 to 500 micrograms every 8 hours for 24 to 72 hours. RESULTS: Treatment was effective in four patients: serum cortisol levels decreased to within or below the normal range in Patients 1, 2, and 3, and ACTH levels were substantially lowered in Patient 4, who had previously been adrenalectomized for a metastatic islet cell tumor. These responses were sustained during long-term treatment for 2 to 72 weeks. All four patients showed no evidence of a pituitary tumor on computed tomographic or magnetic resonance imaging and had proven (Patients 3 and 4) or presumed ectopic disease. Of the six patients who did not respond, four had pituitary tumors and two had presumed ectopic ACTH production. CONCLUSION: We conclude that a short trial of octreotide is warranted in patients with ACTH-dependent Cushing's syndrome who have no demonstrable pituitary tumor. A response to treatment should alert the physician to the possibility of an ectopic ACTH source and will identify patients whose disease may be controllable using octreotide.

Comparison of thyroglobulin and radioiodine scintigraphy during follow-up of patients with differentiated thyroid carcinoma.

OBJECTIVES: To compare serum thyroglobulin concentration and radioiodine scintigraphy during follow-up after thyroidectomy and radioiodine ablation for differentiated, non-medullary thyroid carcinoma. METHODS: One hundred fifty-eight patients received radiation ablation after thyroidectomy every 3-4 months until no pathological radioiodine uptake was seen on the scintigraphy. Simultaneously performed postablation scintigraphy and serum thyroglobulin measurement were related to clinical characteristics and mutually compared using kappa statistics (observed agreement not accounted for by chance divided by possible agreement not accounted for by chance). RESULTS: After three ablation doses, serum thyroglobulin concentration had fallen to below detection limit (5 micrograms/L) in 71% of the patients and 70% of the patients had achieved negative scintigraphy after a median radioiodine dose of 3700 MBq I-131 and a median follow-up time of 5 months. The observed agreement between serum thyroglobulin and scintigraphy after the third ablation dose was 62%. The chance agreement was 50% giving a kappa value of only 24%. The size of the thyroid cancer at admission was larger in patients with a positive scintigraphy after first ablation compared with patients with a negative scintigraphy (p = 0.005) and was correlated to thyroglobulin concentration (p = 0.05). Among patients with thyroglobulin level > 5 micrograms/L after thyroidectomy and first ablation dose, there were more patients who at admission had palpable lymph nodes in the neck (p = 0.06) and microscopically verified neck metastasis (p = 0.03) compared with the group with thyroglobulin < 5 micrograms/L. These differences were not seen when comparing patients with positive and negative scintigraphies. CONCLUSION: The low agreement between the two markers for thyroid cancer emphasizes the value of complementary use of thyroglobulin and scintigraphy in the follow-up of thyroid cancer patients. Patients with large tumours and neck metastasis probably need higher radioiodine doses for complete ablation.

Macroprolactinomas with suprasellar extension: effect of bromocriptine withdrawal during one or more pregnancies.

OBJECTIVE: To investigate the effects of bromocriptine withdrawal during one or more pregnancies in patients who presented with pituitary macroprolactinomas with suprasellar extension. DESIGN: Four infertile patients presenting with a macroprolactinoma with suprasellar extension conceived during treatment with bromocriptine on 10 occasions resulting in eight full-term normal deliveries. Treatment was withheld shortly after conception in each pregnancy. RESULTS: Serum prolactin (PRL) levels fell initially from a mean of 2,776 (range 1,682 to 4,515) to 27 micrograms/L (range 1 to 71) with the development of a partially empty sella in all patients. Recovery of visual field defects occurred in the only affected individual. In case 1, PRL levels remained within the normal range, after bromocriptine withdrawal in the first pregnancy, with the development of an empty sella. Prolactin levels, however, increased substantially in cases 2 to 4. An asymptomatic suprasellar tumor extension returned in cases 2 and 3. After two or more pregnancies (cases 1, 3, and 4), there was a progressive decline in the serum PRL levels. Although still elevated in cases 3 and 4, the PRL levels were considerably below those obtained at presentation or in the first pregnancy. Tumor regression with the development of an empty sella was observed in both these patients as well in their pregnancy or postpartum period. CONCLUSIONS: Bromocriptine may be safely withdrawn during pregnancy in patients presenting with a macroprolactinoma. With multiple bromocriptine induced pregnancies, PRL levels and tumor size may progressively decrease with the eventual development of an empty sella.

Comparison of 1073 MBq and 3700 MBq iodine-131 in postoperative ablation of residual thyroid tissue in patients with differentiated thyroid cancer.

In a randomized prospective study, we compared the efficacy of low dose (1073 MBq) and high dose (3700 MBq) iodine-131 administration in postoperative ablation of residual functioning thyroid tissue in 63 patients with differentiated thyroid cancer. We were unable to demonstrate any difference between the low- and the high-dose of radioactive iodine in scintigraphic ablation of remnant tissue. In 81% (21/26) of the patients, 1073 MBq ablated after the first dose, 77% (21/26 + 3/5 = 24/31) after the first plus second dose, and 69% (24/31 + 0/4 = 24/35) after the first, second, and third dose. Radioiodine (3700 MBq) ablated in 84%, 73%, and 69% of the patients after respectively 1., 1. plus 2., and 1. plus 2. plus 3. dose. Forty percent of the patients ablated with the low dose and 44% ablated with the high dose had elevated thyroglobulin levels at the time of complete scintigraphic ablation. In conclusion, we did not find any difference between 3700 MBq and 1073 MBq iodine-131 as regard to number of doses needed for complete scintigraphic ablation of residual functioning thyroid tissue.

Lung carcinoid with Cushing's syndrome: control of serum ACTH and cortisol levels using SMS 201-995 (sandostatin).

Two patients with Cushing's syndrome due to lung carcinoid tumours were given the long-acting somatostatin analogue SMS 201-995 (Sandostatin). One received a single 50 micrograms dose which produced a 50% reduction in circulating ACTH levels within 4 h. The other has been maintained in clinical and biochemical remission for 10 weeks on 100 micrograms tid. This is the first report of the successful use of SMS 201-995 in carcinoid-induced Cushing's syndrome, and suggests that this hormone analogue could be valuable in the long term medical management of such patients.

The use of SMS 201-995 (somatostatin analogue) in insulinomas. Additional case report and literature review.

A 76-year-old man, a known case of insulinoma, was well controlled for 11 days on 50 micrograms SMS 201-995 every 12 h; clinical recovery was immediate with normalization of blood sugars and C-peptide levels. The potential value of this new drug in the management of insulinomas is illustrated by this case and by 11 additional case reports which are reviewed. A rise in C-peptide levels during treatment without concomitant hypoglycaemia might be the first indication of a loss of control.

One-stage complete genital reconstruction for patients with congenital adrenal hyperplasia.

We performed 1-stage complete genital reconstruction on 20 female subjects with congenital adrenal hyperplasia. The blood and nerve supply to the glans was retained by preserving the neurovascular bundle, as well as the ventral mucosal strip. Preservation of the neurovascular bundle was simplified. The phallic skin was used to form labia minora and a flap vaginoplasty was performed simultaneously. There were no operative complications and all 20 patients had satisfactory results.

Puberty due to a mixed germ cell tumour of the hypothalamus secreting BhCG and alpha-fetoprotein.

A 14 year-old boy presented with visual impairment due to a large suprasellar tumour secreting beta-human chorionic gonadotrophin (BhCG) and alpha-fetoprotein (alpha FP). He was sexually mature with an advanced bone age of 17 years, and suffering from partial hypopituitarism. Treatment with external radiotherapy resulted in a reduction of tumour size and fall of the serum testosterone BhCG and alpha FP levels. We conclude that pubertal development had been initiated and maintained by ectopic hCG production from his intracerebral mixed germ cell tumour. Patients with tumours in the pineal and suprasellar regions should be screened for elevated levels of BhCG and alpha FP. We suspect that many of these tumours cause precocious puberty by secreting BhCG.

Male hypothalamic hypogonadism: induction of spermatogenesis by subcutaneous pulsatile gonadotrophin-releasing hormone.

Six male patients (aged 21-34 years) with isolated hypothalamic hypogonadism were given subcutaneous pulses of gonadotrophin-releasing hormone every 90 min for 14-74 weeks. The therapy produced an increase in testicular volume (4 patients) and a rise in serum luteinizing hormone, follicle-stimulating hormone, and testosterone levels in every patient. Motile sperm developed in 3 patients after a mean of 17 weeks, but were not seen in other patients who were less sexually developed after a mean of 31 weeks of therapy. Computerized tomography scans of the pituitary fossa revealed an empty sella in 4 patients and a partially empty sella in 2. Subcutaneous pulsing of gonadotrophin-releasing hormone is a simple and safe way of inducing spermatogenesis, but it is more likely to be successful in patients whose pubertal development is otherwise near completion. Previous human chorionic gonadotrophin and/or testosterone treatment does not interfere with and may benefit subsequent gonadotrophin-releasing hormone therapy.

Hereditary resistance to 1,25-dihydroxyvitamin D: clinical and radiological improvement during high-dose oral calcium therapy.

A 6-year-old boy, of consanguinous parents, presented with severe rickets and alopecia; he was found to have hypocalcaemia and elevated circulating 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels. He showed no calcaemic response to 1,25-(OH)2D3 or ergocalciferol given for 3 or more months in daily doses as high as 48 micrograms and 6 X 10(6) IU, respectively. Analyses with cultured skin fibroblasts revealed a normal capacity and affinity for 1,25-(OH)2D3 in soluble extracts ('cytosol') and in nuclei of intact cells but no detectable response of 25-(OH)D3 24-hydroxylase to 1,25-(OH)2D3 in high concentration. Treatment with high doses of calcium (3-4 g elemental calcium orally per day) produced a striking clinical and radiological improvement. We conclude that high oral doses of calcium can replace many of the actions of calciferols. Therapy with high doses of calcium should be tried in similarly affected cases that appear totally or partially unresponsive to calciferols.

Pattern of calcium metabolism in normo- and hypercalciuric patients with calcium urolithiasis in Saudi Arabia.

Urinary calcium excretion was measured in 100 consecutive normocalcemic patients with calcium urolithiasis and 12 Saudi Arabian controls while the patients and the controls were eating their usual diet of unknown calcium content. Only 16 patients were hypercalciuric using the definition of twenty-four-hour urinary calcium of more than 300 mg for males and more than 250 mg for females, and one of these patients was subsequently found to have hyperparathyroidism. The twenty-four-hour urine calcium was less than 200 mg in 60 per cent of male patients and in all the male controls. Since the dietary intake of calcium during the twenty-four-hour urinary collection was unknown, a 1,000-mg calcium loading test was performed in an attempt to differentiate various patterns of abnormal calcium excretion. Of the twenty-four-hour normocalciuric patients 10 (18%) had "absorptive hypercalciuria" and 16 patients (29%) demonstrated a "renal hypercalciuria" pattern. Thirty-nine patients (57%) and all 12 controls had normocalciuria before and after calcium loading.

Prolactin levels in pregnancy: comparison of normal subjects with patients having micro- or macroadenomas after early bromocriptine withdrawal.

14 previously infertile patients, 11 with radiologically abnormal fossae, and a mean prolactin level of 761 ng/ml (range 49-4,500 ng/ml) conceived on 19 occasions during bromocriptine treatment. So far, 15 healthy infants have been delivered. Treatment was withdrawn soon after conception and the subsequent prolactin changes compared with those of 44 normal subjects. Prolactin levels returned to pretreatment values in 7, but stayed within our normal range (less than 350 ng/ml) in the 6 remaining patients studied. No patient developed signs or symptoms of tumor enlargement. 2 patients, 1 of them with the largest tumor, have now normal prolactin levels and can be considered as cured. Bromocriptine treatment can restore fertility and be safely withdrawn during pregnancy even in patients presenting with large tumors. Nevertheless, patients should be carefully monitored and treatment with bromocriptine re-introduced if necessary.

Hypothalamic hypogonadism: induction of ovulation and pregnancy by subcutaneous pulsatile injections of gonadotrophin-releasing hormone.

5 female patients with isolated hypothalamic hypogonadism were given subcutaneous pulses of gonadotrophin-releasing hormone (GnRH), 2.5-15 micrograms every 90 min, for 2-6 months by means of an automated pump. This treatment produced an increase in serum LH, FSH, and estradiol levels in 4 patients, all of whom became pregnant. The estradiol levels failed to rise in 1 patient, in spite of an adequate LH and FSH response, and a subsequent biopsy showed evidence of primary ovarian failure in addition to the hypothalamic deficit. We conclude that subcutaneous pulsatile GnRH administration is a simple, safe, and relatively inexpensive way to induce ovulation in patients with hypothalamic hypogonadism.

A syndrome of hypogonadism, alopecia, diabetes mellitus, mental retardation, deafness, and ECG abnormalities.

A distinct and previously undescribed syndrome has been observed in six Saudi Arabian patients from two highly inbred families. The parents were normal, indicating an autosomal recessive pattern of inheritance. All the patients have a distinctive facial appearance, hypogonadism, sparse or absent hair, diabetes mellitus, mental retardation, mild deafness, and variable S-T and T wave abnormalities on the electrocardiograph.