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M C Skarulis

Publications and source records attributed to M C Skarulis.

53 records · Page 3Linked to original sources
PubMed1996

Prevalence and mechanisms of hearing loss in patients with resistance to thyroid hormone.

Hearing impairment was anecdotally reported in resistance to thyroid hormone (RTH), a condition caused by mutations in the beta-thyroid hormone receptor (beta TR) gene. Because of its ontogenic distribution in the cochlea, the beta TR may have a pivotal role in the development of auditory function. To assess the prevalence and mechanisms of hearing impairment in RTH, 82 RTH-positive (RTH+) patients and 55 unaffected relatives (RTH-) underwent systematic audiological examination, including puretone and speech reception thresholds, and tests studying middle ear (tympanometry and acoustic reflexes), cochlear (otoacoustic emissions), and retrocochlear integrity (brain stem auditory evoked potentials). Significant hearing loss was present in 21% of RTH+ patients vs. none in RTH- patients. More RTH+ patients had abnormal tympanometry (34% vs. 12%) and abnormal acoustic reflexes (39% vs. 19%). Isolated conductive deficit was found in 7 of 17 RTH+ patients with hearing loss, isolated sensorineural deficit in 7 cases, and mixed deficit in 3 cases. Cochlear dysfunction was found in 50% of all RTH+ patients, with or without hearing loss. Retrocochlear function was normal. No morphological cochlear abnormalities were detected on computed tomography of the temporal bone. In conclusion, hearing loss is a significant problem in RTH, with an equal frequency of conductive (probably related to the frequent ear infections) and sensorineural deficits. Abnormal otoacoustic emissions suggest that the mutant beta TR has a specific negative impact on cochlear function.

Adult↗
PubMed1996

False-positive iodine-131 whole-body scans due to cholecystitis and sebaceous cyst.

False-positive whole-body 131I scans are not frequent but have serious consequences in the management of patients with thyroid cancer. They can be classified in four main groups: elimination of iodine in body fluids, infection or inflammation, cysts or transudates and nonthyroid tumors. We report on two patients with false-positive post-therapy 131I scans. The first patient had uptake projected in the right pelvic area which was later proven to be a large gluteal sebaceous cyst. The second patient had uptake in the gallbladder area that did not disappear after 131I treatment; she underwent exploratory laparotomy which revealed extensive chronic cholecystitis. These cases illustrate two new causes of false-positive 131I whole-body scans (sebaceous cyst and cholecystitis), which highlights two mechanisms (elimination in body fluid and inflammation).

Adenocarcinoma, Follicular↗
PubMed1995

Genetic and clinical features of 42 kindreds with resistance to thyroid hormone. The National Institutes of Health Prospective Study.

OBJECTIVE: To determine the genetic and clinical features of resistance to thyroid hormone in a study from a single institution. DESIGN: Prospective, controlled study. SETTING: National Institutes of Health. PATIENTS: 104 patients with resistance to thyroid hormone from 42 kindreds and 114 unaffected relatives sharing the patients' environmental and genetic backgrounds. MEASUREMENTS: Thyroid, cardiovascular, psychometric, hearing, speech, and growth testing; thyroid tests done at baseline and after TSH-releasing hormone stimulation; and DNA analysis for detection of mutations in the thyroid hormone receptor beta (TR beta) gene (exons 9 and 10). Assessment of tissue-specific compensation for resistance. RESULTS: Inheritance was autosomal dominant in 22 families, sporadic in 14 families, and unknown in 6 families. We found mutations in 25 kindreds (64 patients); 16 mutations were in exon 9 and 9 were in exon 10 of the TR beta gene. In persons with resistance to thyroid hormone, we measured the increased incidence of goiter (65%), attention-deficit hyperactivity disorder (60%), IQ less than 85 (38%), speech impediment (35%), and short stature (18%). We also described new clinical features, such as frequent ear, nose, and throat infections (56%); low weight-for-height in children (32%); hearing loss (21%); and cardiac abnormalities (18%). Genotype, age, whether the mother had resistance to thyroid hormone, and sex influenced the phenotype. Tissue resistance varied from kindred to kindred and involved, in decreasing order, the pituitary gland, the brain, the bone, the liver, and the heart. CONCLUSIONS: This study underscores the incidence of classic features of resistance to thyroid hormone, describes new clinical characteristics of this condition for the first time, and stresses the heterogeneity of the phenotype.

Adolescent↗
PubMed1995

Localization of insulinomas to regions of the pancreas by intra-arterial stimulation with calcium.

OBJECTIVE: To determine the sensitivity of calcium injected into pancreatic arteries in localizing insulin-secreting tumors to regions of the pancreas. DESIGN AND PATIENTS: To stimulate the release of insulin, 25 patients with surgically proven insulinomas (average diameter, 15 mm) had calcium gluconate (0.025 mEq Ca++/kg body weight) injected before surgery into the arteries supplying the pancreatic head (gastroduodenal and superior mesenteric arteries) and the body and tail (splenic artery) of the pancreas. SETTING: Tertiary referral hospital. MEASUREMENTS: Insulin levels were measured in samples taken from the right and left hepatic veins before and 30, 60, and 120 seconds after calcium injection. A twofold increase in insulin level in the sample taken from the right hepatic vein 30 or 60 seconds after injection localized the insulinoma to the segment of the pancreas supplied by the selectively injected artery. Localization done using calcium stimulation was compared with localization done using transcutaneous ultrasonography (n = 22), computed tomography (n = 23), magnetic resonance imaging (n = 21), arteriography (n = 25), and portal venous sampling (n = 9). RESULTS: Calcium stimulation localized 22 of 25 insulinomas (sensitivity, 88% [95% CI, 68% to 97%]) to the correct region of the pancreas. The sensitivities of the other imaging methods were 9% for ultrasonography (CI, 1% to 23%), 17% for computed tomography (CI, 5% to 39%), 43% for magnetic resonance imaging (CI, 22% to 66%), 36% for arteriography (CI, 18% to 57%), and 67% for portal venous sampling (CI, 30% to 93%). Calcium stimulation added only a few minutes to the time needed for pancreatic arteriography and caused no morbid conditions. CONCLUSION: Intra-arterial calcium stimulation with right hepatic vein sampling for insulin gradients is the most sensitive preoperative test for localizing insulinomas.

Adult↗
PubMed1995

Ultrasound-guided fine-needle aspiration of parathyroid lesions: a morphological and immunocytochemical approach.

Ultrasound-guided (US) fine-needle aspiration (FNA) can successfully localize abnormal parathyroid tissue (PT) preoperatively in hyperparathyroid patients. Samples from 12 patients with primary hyperparathyroidism evaluated using this technique since 1990 at the National Institutes of Health form the basis of this report. Eleven patients had undergone previous parathyroid surgery that failed to correct their hyperparathyroidism. Cytological evaluation and C-terminal (midmolecule) parathyroid hormone radioimmunoassay (PTH RIA) were performed on all samples. When sufficient material was available, immunocytochemical stains for chromogranin and thyroglobulin were performed. All cytological diagnoses were made with-out knowledge of the PTH RIA results. Using a combined approach of cytology and immunocytochemistry, six of 12 of the samples (50%) were diagnosed as PT. Follow-up on these six patients was confirmatory. Four of 12 samples (33%) were identified as thyroid; one of these patients had a PT adenoma identified in another location (the remaining three patients await further localization studies). Two of 12 samples (17%) could not be diagnosed because of insufficient cellularity; in both patients PT lesions were found in other locations. Morphological features of PT in FNA include the presence of cellular tissue fragments with epithelial cells arranged perivascularly around capillary cores, an overall organoid or trabecular architecture, and frequent microacini. Parathyroid tissue cells have round, fairly uniform nuclei measuring 6 to 8 microns. Clusters of larger oxyphil cells may show considerable anisonucleosis. The absence of features of thyroid tissue such as hemosiderin-laden macrophages, abundant colloid, and paravacuolar granules is significant. However, in cases of intrathyroidal PT, admixed thyroid material included in the aspiration tract may be present immunocytochemical stains for chromogranin, which is present in parathyroid tissue but not thyroid follicular cells, were positive in six of six samples interpreted as PT by cytology. No thyroglobulin staining was observed in any of the four of six PT samples for which material was available. C-terminal (midmolecule) PTH RIA correlated with cytological diagnoses in 100% of samples. Parathyroid hormone levels ranged from 1,300 to 262,000 pg/mL (normal blood level, 50 to 340 pg/mL) in the six samples diagnosed as PT by cytology. Parathyroid hormone RIA levels in the six non-PT samples were below normal blood values. The combined approach of cytology and immunocytochemistry provides high diagnostic accuracy in the interpretation of US-guided FNA for preoperative localization of parathyroid tissue.

Adult↗
PubMed1995

Tc-99m sestamibi imaging of a hyperfunctioning parathyroid autograft with Doppler ultrasound and MRI correlation.

The authors describe a case in which Tc-99m sestamibi demonstrated increased vascularity and uptake in a hyperfunctioning autograft in a patient with recurrent hyperparathyroidism and multiple endocrine neoplasia type 1. Findings were confirmed by differential parathyroid hormone levels in antecubital venous blood samples, ultrasound with color Doppler, MRI, and surgery.

Female↗
PubMed1995

High cervical intravagal hypercellular parathyroid gland as the etiology of severe persistent primary hyperparathyroidism.

The preoperative localization and operative management of a high cervical intravagal parathyroid adenoma in a young woman with severe persistent primary hyperparathyroidism is presented. The etiology of persistent hyperparathyroidism is most frequently a missed adenoma that is often in an ectopic location; of these, undescended adenomas represent a small but important proportion. If clinical suspicion and preoperative localization procedures suggest an undescended gland, a direct surgical approach using a high cervical incision and a unilateral exploration is often successful.

Adenoma↗
PubMed1995

Technetium-99m-sestamibi imaging before reoperation for primary hyperparathyroidism.

UNLABELLED: Recent studies have reported high sensitivities for parathyroid localization with 99mTc-sestamibi and have been performed using either 123I/99mTc-sestamibi or a double-phase sestamibi scanning technique. These studies have focused primarily on patients undergoing initial surgery. We studied 35 patients prior to reoperative surgery to investigate the relative sensitivities of these two technique sin this patient population. METHODS: Double-phase sestamibi scanning (early and delayed imaging) was performed in all patients. Evaluable 123I/99mTc-sestamibi subtraction studies were also obtained in 25 patients. Results were correlated with surgical findings in 32 patients and with clinical outcome in 3 patients in whom mediastinal lesions were radiographically ablated. RESULTS: Overall, double-phase sestamibi imaging detected 23 of 39 abnormal parathyroid glands (59%), whereas 123I/99mTc-sestamibi detected 19 of 27 (70%). Oblique imaging, delayed imaging and 123I subtraction all contributed to sensitivity, and 123I subtraction also proved useful in patients with partial thyroid suppression. Two patients had lesions visible on the early sestamibi images that were not seen at all on the delayed scans. There were four false-positive findings. CONCLUSION: No significant differences between double-phase sestamibi and 123I/99mTc-sestamibi subtraction scanning were found, although the latter tended to be more sensitive.

Adenoma↗
PubMed1994

Use of preoperative fine-needle aspiration in patients undergoing reoperation for primary hyperparathyroidism.

BACKGROUND: Neck reexploration for primary hyperparathyroidism has a lower success rate and greater morbidity than initial exploration because of scarring and distortion of tissue planes and the possibility of a parathyroid neoplasm located in an ectopic or unusual position. Although the use of standard noninvasive imaging studies for reoperative parathyroid surgical procedure is well accepted, the use of invasive studies to localize parathyroid neoplasms, particularly percutaneous aspiration of potential lesions, is controversial. In this report we analyze the results and morbidity in patients undergoing fine-needle aspiration before neck reexploration. METHODS: From 1982 to 1993, 255 patients underwent reexploration for persistent or recurrent hyperparathyroidism at the National Institutes of Health. Of these 255 patients 42 underwent 44 preoperative fine-needle aspirations by ultrasonography or computed tomography guidance in an attempt to localize a parathyroid neoplasm. The aspirated contents were then analyzed for parathyroid hormone content. RESULTS: Of the 44 aspirations 26 (59%) were true positives with no false positives. Of 18 negative fine-needle aspirations, 11 (25%) were false negatives, and seven (16%) were true negatives. The specificity and sensitivity of percutaneous fine-needle aspiration were 100% and 70%, respectively. CONCLUSIONS: Percutaneous fine-needle aspiration for parathyroid hormone is a safe, well-tolerated technique that is highly specific and allows a directed surgical resection avoiding further invasive workup when the aspirate is positive.

Adult↗
PubMed1994

Localization and operative management of undescended parathyroid adenomas in patients with persistent primary hyperparathyroidism.

BACKGROUND: Between 5% and 10% of patients who undergo cervical exploration for primary hyperparathyroidism will have persistent or recurrent hyperparathyroidism. Many of these patients have parathyroid tumors in unusual locations. One such site of ectopic parathyroid tissue is an undescended parathyroid adenoma at or superior to the carotid bifurcation. We describe our experience with the preoperative localization and surgical management of undescended parathyroid adenomas. METHODS: From 1982 to 1993 a consecutive series of 255 patients have undergone localization studies and surgical exploration for persistent or recurrent hyperparathyroidism at the Clinical Center of the National Institutes of Health. Operative strategy was determined by review of the patient's surgical history, disease reports, and data from localizing studies. Patients with an undescended parathyroid adenoma identified before the operation were examined with a direct approach high in the neck. Patients who did not have definitive preoperative localization were explored with the previous transverse cervical incision. RESULTS: Seventeen undescended parathyroid adenomas were identified in 255 patients. Thirteen (76%) of 17 patients had an undescended parathyroid adenoma precisely localized before the operation and were examined via a limited, oblique incision high in the neck anterior to the sternocleidomastoid muscle. In the 13 patients who had undergone accurate localization before the operation, the median operative time was 75 minutes compared with 235 minutes for four patients who did not have an undescended parathyroid adenoma identified before the operation and were examined via a previous transverse cervical incision. All patients were cured of their hyperparathyroidism. CONCLUSIONS: Undescended parathyroid adenomas were the cause of failed cervical exploration in 17 (7%) of 255 patients. Accurate preoperative localization of these lesions is possible in most cases with a combination of noninvasive and invasive modalities. Successful preoperative localization can convert a prolonged exploration of the neck and mediastinum into a brief, curative procedure with minimal morbidity.

Adenoma↗
PubMed1993

Prospective evaluation of selective venous sampling for parathyroid hormone concentration in patients undergoing reoperations for primary hyperparathyroidism.

BACKGROUND: The utility of standard radiologic imaging studies in guiding reoperative parathyroid surgery for primary hyperparathyroidism is widely known and accepted. The additional information gained by selective venous sampling in that patient population has not been well defined. We report the results of our experience with this method. METHODS: Between 1982 and 1992, 223 consecutive patients underwent reoperations for persistent or recurrent primary hyperparathyroidism after a prospectively determined series of imaging studies. Patients underwent noninvasive testing consisting of ultrasonography, computed tomography, technetium thallium scanning, and magnetic resonance imaging. Patients with negative, equivocal, or discordant results on the noninvasive studies proceeded to angiography. If angiography was negative, selective venous sampling was performed. RESULTS: Eighty-six patients (39%) with negative or equivocal noninvasive test and angiogram results underwent selective venous sampling. Seventy-six patients (88%) had a significant gradient in levels of parathyroid hormone from veins draining the left side of the neck (n = 25), the right side of the neck (n = 33), both sides of the neck (n = 7), and the thymus (n = 11). Correlation of these findings with operative findings revealed a sensitivity of 88% and a specificity of 86%. In the subgroup of patients who underwent venous sampling and had completely negative results of standard radiologic studies (35 of 86; 40%), 28 patients (80%) had venous gradients and seven patients (20%) had no gradient. Of those 28 patients in whom the venous sampling gradients were the only positive localization study, the venous samplings were helpful in 23 patients (true positive gradients), and the operative success rate was 93%. In the seven patients with no positive preoperative localizing studies including venous sampling, there were two operative failures (operative success, 71%). CONCLUSIONS: Our results show that selective venous sampling is a highly sensitive and specific method to regionally localize abnormal parathyroid glands not imaged by standard noninvasive and invasive radiologic techniques. Venous sampling is the study of choice in guiding reoperative procedures for occult abnormal parathyroid glands that are undetected despite the use of all available imaging studies.

Diagnostic Imaging↗
PubMed1992

Glycosylation changes in human chorionic gonadotropin and free alpha subunit as gestation progresses.

Carbohydrate is important to the structure, function, and circulatory survival of the glycoprotein hormones. Human CG (hCG) and the related free alpha-molecule of pregnancy contain four and two asparagine-linked oligosaccharides, respectively. The present study analyzes changes in the glycosylation patterns of hCG and free alpha in early vs. late gestation. Five volunteers provided 24-h urine samples, weekly, throughout their pregnancies. Extracts of early pregnancy (weeks 7-12) and late pregnancy (weeks 28-32) urines were pooled. Early and late samples from each patient were subjected to gel filtration to separate hCG and free alpha, and the populations thus obtained were analyzed by lectin affinity chromatography on Concanavalin A-Sepharose (Con A) and Lens culinaris-agarose (Lch). Using Con A, free alpha and hCG were separated into an unbound fraction (eluted with Con A buffer), a weakly bound fraction (eluted with 10 mmol alpha-methyl-D-glucoside) and a tightly bound fraction (eluted with 500 mmol alpha-methyl-D-mannoside). For free alpha-molecule, a significant decrease in tightly bound Con A forms, was noted from early to late pregnancy with a mean difference of 17.0 +/- 2.4% (P less than 0.01). Concomitantly, in late pregnancy, an increase in Con A unbound forms of free alpha was noted with mean difference of 12.5 +/- 1.7% (P less than 0.01). These changes indicate the presence of more highly branched oligosaccharides on free alpha as gestation advances. No changes were noted in the Con A binding of intact hCG; nearly all hCG bound in both early and late pregnancy. Using Lch, free alpha and hCG were separated into an unbound fraction (eluted with Lch buffer) and a bound fraction (eluted with 500 mmol alpha-methyl-D-mannose). Both free alpha and intact hCG in late pregnancy exhibited increased binding to Lch, with mean differences from early to late pregnancy of 30.2 +/- 4.8% (P less than 0.01) and 11.4 +/- 4.5% (P less than 0.05), respectively. These data indicate increased incorporation of fucose into the carbohydrate moieties in late pregnancy. Taken together, these data derived by analysis using lectin specificity imply the presence of more highly branched, fucosylated oligosaccharides as gestation progresses.

Chorionic Gonadotropin↗
PubMed1991

Free alpha molecules from pregnancy stimulate secretion of prolactin from human decidual cells: a novel function for free alpha in pregnancy.

Free alpha molecules isolated from pregnancy, as well as highly purified reference preparations of hCG alpha subunit (CR119 or CR123), stimulated the release of prolactin from human decidual cells in culture. The amount of prolactin secreted during a 24 h incubation was concentration-dependent over a range of increasing doses of alpha from 0.2 to 20 ng/ml with an ED50 of about 1.6 ng/ml. These concentrations are well within the physiologic maternal serum free alpha levels which average 350 ng/ml during the third trimester of pregnancy. Incubation of decidual cells with a reference preparation of intact hCG (CR123) at a concentration of 260 ng/ml resulted in stimulated secretion of prolactin, however, the observed stimulation could be attributed to contamination of the preparation with free alpha or dissociated hCG alpha subunit. Purified hCG beta subunit had no stimulatory activity on the decidual cell culture. The effect of alpha subunit on the stimulated release of prolactin was not due to a generalized stimulation of protein synthesis and secretion since no increase was observed in the release of 35S-labeled proteins compared to controls. In addition, the observed increase in prolactin secretion was not due to a toxic effect of the alpha subunit since there was no visible effect on cell viability, and the cellular enzymes, LDH and alkaline phosphatase, were not detected in the culture medium. Addition of exogenous hCG alpha subunit to primary cultures of human trophoblast cultures did not result in stimulated release of human placental lactogen. We conclude that free alpha molecules of pregnancy stimulate release of prolactin from human decidual cells in culture. These results suggest a novel role for free alpha in the paracrine regulation of decidual prolactin secretion.

Cells, Cultured↗
PubMedDate not supplied

Sonography of gallbladder abnormalities in acromegaly patients following octreotide and ursodiol therapy: incidence and time course.

PURPOSE: We studied the effects of octreotide and ursodiol on the gallbladders of patients with acromegaly. METHODS: We performed gallbladder sonography in patients with acromegaly at various intervals during treatment. Group I (18 patients) was treated with subcutaneous injections of the somatostatin analogue octreotide. Group II (10 patients) was treated with ursodiol while receiving octreotide therapy. RESULTS: Seventy-eight percent of patients receiving octreotide developed gallbladder abnormalities: sludge in 72% (13/18) and calculi in 39% (7/18). Ursodiol reversed the gallbladder abnormalities in 7 of 10 patients. CONCLUSIONS: A majority of patients receiving octreotide develop gallbladder abnormalities. Ursodiol appears to reverse the abnormalities in most cases.

Acromegaly↗
PubMedDate not supplied

Multiple endocrine neoplasia type 1: new clinical and basic findings.

Multiple endocrine neoplasia type 1 (MEN1) provides a prime example of how a rare disease can advance our understanding of basic cell biology, neoplasia and common endocrine tumors. MEN1 is expressed mainly as parathyroid, enteropancreatic neuroendocrine, anterior pituitary and foregut carcinoid tumors. It is an autosomal dominant disease caused by mutation of the MEN1 gene. Since its identification, the MEN1 gene has been implicated in many common endocrine and non-endocrine tumors. This is a brief overview of recent scientific advances relating to MEN1, including newly recognized clinical features that are now better characterized by genetic analysis, insights into the function of the MEN1-encoded protein menin, and refined recommendations for mutation testing and tumor screening, which highlight our increasing understanding of this complex syndrome.

Adrenal Cortex Neoplasms↗