Handwriting characteristics in patients with overt autoimmune hypothyroidism: a prospective case-control study.

PURPOSE: Previous studies have demonstrated handwriting changes in patients with overt hyperthyroidism due to Graves' disease. The aim of the present study was to investigate handwriting features in patients affected by overt autoimmune hypothyroidism. METHODS: Thirty subjects - 24 females and 6 males, mean and median age of 50.15 ± 16.8 years and 52.5 years, respectively - with overt hypothyroidism (OH) related to Hashimoto's thyroiditis (Group 1), and 30 age- and sex-matched euthyroid individuals (Group 2) were recruited to write a "standard text". Group 1 patients repeated the text once the euthyroid state was reached on L-T4 substitution therapy. Group 2 subjects wrote the text again 1 to 4 weeks thereafter. The letters underwent a detailed analysis by a handwriting expert, through inspection, a stereoscopic microscope and a magnifying glass. Furthermore, the time that both Groups took to go through with the text was clocked. RESULTS: None of the handwriting variables differed significantly within each Group and between the two Groups. Hypothyroid patients took significantly more time to go through with the text compared to the time taken once they became euthyroid (3.29 ± 1.66 vs 2.63 ± 1.55 minutes, respectively) and the time taken by the control group (p < 0.01). Of note, three Group 1 patients missed to copy some words or even whole sentences on the paper while they were overtly hypothyroid. CONCLUSIONS: The present study demonstrates that handwriting speed is able to disclose the impact of thyroid hormone deficiency on the central nervous system's functions. In particular, the longer time taken to go through with the text and the sentences missed by some hypothyroid patients, are the counterpart of psychomotor slowdown, impaired attention and memory loss peculiar to OH.

Uncommon clinical presentations of pheochromocytoma and paraganglioma in two different patients affected by two distinct novel VHL germline mutations.

CONTEXT: The von Hippel-Lindau (VHL) syndrome is an inherited multitumour disorder characterized by clinical heterogeneity and high penetrance. Pheochromocytoma (Pheo) is present in 10%-15% of cases and can be isolated or associated with other lesions such as haemangioblastomas, kidney cysts or cancer and pancreatic lesions. In VHL patients, Pheos generally secrete norepinephrine and are located in the adrenals. Extra-adrenal Pheos (paragangliomas, PGLs) are rare. OBJECTIVE: While performing genetic testing in patients affected by apparently sporadic Pheos or PGLs, we found two novel different VHL germline mutations in two females who presented with two distinct very uncommon clinical pictures. One patient was studied for the presence of an adrenal incidentaloma and the other for the presence of a neck tumour. METHODS AND RESULTS: Patients coding regions and exon-intron boundaries of RET (exons 10, 11, 13-15), VHL, SDHD, SDHB and SDHC genes were amplified and sequenced. We identified two novel VHL point mutations: a L198V missense mutation in a 32-year-old female affected by a right adrenal compound and mixed tumour constituted by an epinephrine secreting Pheo, a ganglioneuroma and an adrenocortical adenoma, and a T152I missense mutation in a 24-year-old female affected by a left carotid body tumour. No other lesions were found in the patients or in the VHL mutation positive relatives. CONCLUSIONS: These cases enlarge the list of VHL mutations and add new insights in the clinical variability of VHL disease, thus confirming the importance of genetic testing in patients affected by apparently sporadic Pheos or PGLs.