Objective: Our aim was to report the recent changes in diagnosis and management of TSH-secreting pituitary adenomas. Methods: We retrieved 43 consecutive patients with TSH-secreting pituitary tumors (23 male and 20 female) among 4400 pituitary adenomas followed between 1976 and 2001 in six Belgian and French centers. Results: TSH was elevated in 18/43 and a subunit in 13/32 patients. In patients with intact thyroid ðn ¼ 30Þ; mean free tri-iodothyronine was 13.1 pmol/l (range 3.5-23) and mean free thyroxine was 38.4 pmol/l (range 10.2 -62.7). Hyperprolactinemia and acromegaly were associated in 9/43 and 8/43 cases. The number of associated hypersecretions was higher in macroadenomas than in microadenomas (Chi square = 11.2, P , 0:01). Two women had sporadic multiple endocrine neoplasia type 1-associated syndrome. The proportion of microadenomas versus macroadenomas was 1/11 (period 1974-1986) and 8/32 (period 1987 -2001). Bilateral petrosal sinus sampling, 111 In-pentreotide scintigraphy and ( 11 C)-L-methionine positron emission tomography scan confirmed diagnosis in four questionable microadenomas. Macroadenomas with extrasellar extension (31 cases) had a tendency to be medially located. Medical treatment with somatostatin analogs was initiated as first-line treatment in 26 patients. TSH levels were reduced by more than 50% in 23/26 cases. A tumoral shrinkage of more than 20% was observed in 5/13 cases. Surgery was performed in 36 patients. After 1 year, 21 of them (58.3%) met the criteria of surgical favorable outcome. Pituitary radiotherapy ðn ¼ 8Þ and somatostatin analogs allowed normalization in cases not cured by surgery. Conclusion: Ultrasensitive methods for TSH measurement led to an earlier recognition of TSH-secreting pituitary tumors. In this series, we observed that TSH-secreting pituitary tumors are today more frequently found at the stage of microadenomas, medially located, without associated hypersecretions and needing new exploration methods as compared with older series. This changing spectrum in the presentation of TSH-secreting pituitary tumors and the excellent response to somatostatin analogs has been accompanied by an improvement in the prognosis of the disease.

In these LMNA-linked lipodystrophic patients, the prevalence of PCOS, infertility, and gestational diabetes was higher than in the general population. Moreover, the prevalence of gestational diabetes and miscarriages was higher in lipodystrophic LMNA-mutated women than previously reported in PCOS women with similar body mass index. Women with lipodystrophies due to LMNA mutations are at high risk of infertility, gestational diabetes, and obstetrical complications and require reinforced gynecological and obstetrical care.

PCOS was associated with a significant decrease of insulin sensitivity, independent of obesity. The correlation between LH and insulin sensitivity suggests a complementary action in PCOS.

Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome characterized by fetal macrosomia, macroglossia, and abdominal wall defects. BWS patients are at risk to develop Wilms tumor, neuroblastoma, hepatoblastoma, and adrenal tumors. A young woman with BWS features, but with inconclusive genetic evidence for the disease, came to clinical observation for signs of virilization at the age of 16 years. An adrenocortical tumor was diagnosed and surgically resected. The tumor underwent 2 local relapses that were also surgically treated. The patient was also operated to remove a breast fibroadenoma. SNP arrays were used to analyze chromosome abnormalities in normal and tumor samples from the patient and her parents. The patient presented genome-wide mosaic paternal uniparental disomy (patUPD) both in the adrenocortical and the breast tumors, with different degrees of loss of heterozygosity (LOH). The more recent relapses of the adrenocortical tumor showed a loss of part of chromosome 17p that was absent in the first tumor. Analysis of a skin biopsy sample also showed mosaic patUPD with partial LOH, while no LOH was detected in leukocyte DNA. This case shows that virilizing adrenocortical tumors may be a clinical feature of patients with BWS. The SNP array technology is useful to diagnose genome-wide patUPD mosaicism in BWS patients with an inconclusive molecular diagnosis and underlines the tumorigenic potential of the absence of the maternal genome combined with an excess of the paternal genome.