Biomedical subjects

Jacqueline Jonklaas

Publications and source records attributed to Jacqueline Jonklaas.

10 recordsLinked to original sources

PubMed2006

Use of steroid profiles in determining the cause of adrenal insufficiency.

HYPOTHESIS: A cortisol response to adrenocorticotropin injection is the standard test for diagnosing adrenal insufficiency. Multiple steroid hormones can now be accurately measured by tandem mass spectrometry in a single sample. The study objective was to determine whether a steroid profile, created by simultaneous measurement of 10 steroid hormones by tandem mass spectrometry, would help determine the cause of adrenal insufficiency. DESIGN: A 10-steroid profile was measured by tandem mass spectrometry during the performance of a standard high dose cortrosyn stimulation test. The steroids were measured at baseline, 30, and 60min following synthetic adrenocorticotropin injection. Adrenal insufficiency was defined as a peak cortisol level of less than 20microg/dL. Testing was conducted in the general clinical research center of a university medical center. Normal volunteers, patients suspected of having adrenal insufficiency, and patients with known adrenal insufficiency participated. RESULTS: Our results showed that adrenal insufficiency of any cause was adequately diagnosed using the response of 11-deoxycortisol, dehydroepiandrosterone, or these analytes combined in a two-steroid profile. A three-steroid profile yielded a test with 100% accuracy for discriminating primary adrenal insufficiency from normal status. Primary adrenal insufficiency was well separated from secondary adrenal insufficiency using only a single aldosterone value. 11-Deoxycortisol, dehydroepiandrosterone, and a two-steroid profile each provided fair discrimination between secondary adrenal insufficiency and normal status. CONCLUSIONS: We conclude that stimulated levels of aldosterone, 11-deoxycortisol, dehydroepiandrosterone, and a two- or three-steroid profile provided additional discrimination between states of adrenal sufficiency and insufficiency. It is proposed that a steroid profile measuring cortisol, aldosterone, 11-deoxycortisol, and dehydroepiandrosterone would potentially improve the ability to determine the cause of adrenal insufficiency.

Adrenal Cortex Hormones↗

PubMed2006

Outcomes of patients with differentiated thyroid carcinoma following initial therapy.

This analysis was performed to determine the effect of initial therapy on the outcomes of thyroid cancer patients. The study setting was a prospectively followed multi-institutional registry. Patients were stratified as low risk (stages I and II) or high risk (stages III and IV). Treatments employed included near-total thyroidectomy, administration of radioactive iodine, and thyroid hormone suppression therapy. Outcome measures were overall survival, disease-specific survival, and disease-free survival. Near-total thyroidectomy, radioactive iodine, and aggressive thyroid hormone suppression therapy were each independently associated with longer overall survival in high-risk patients. Near-total thyroidectomy followed by radioactive iodine therapy, and moderate thyroid hormone suppression therapy, both predicted improved overall survival in stage II patients. No treatment modality, including lack of radioactive iodine, was associated with altered survival in stage I patients. Based on our overall survival data, we confirm that near-total thyroidectomy is indicated in high-risk patients. We also conclude that radioactive iodine therapy is beneficial for stage II, III, and IV patients. Importantly, we show for the first time that superior outcomes are associated with aggressive thyroid hormone suppression therapy in high-risk patients, but are achieved with modest suppression in stage II patients. We were unable to show any impact, positive or negative, of specific therapies in stage I patients.

Adenocarcinoma, Follicular↗

PubMed2006

Intravenous methimazole in the treatment of refractory hyperthyroidism.

BACKGROUND: Management of a hyperthyroid patient unable to take oral or rectal medication is a difficult clinical problem. The need for an alternative parenteral route of antithyroid medication administration in thyrotoxic patients occurs in certain rare cases, such as emergent gastrointestinal surgery, bowel ileus or obstruction, or severe vomiting and diarrhea. We report a simple and successful protocol for the preparation and use of intravenous methimazole (MMI) for treatment of hyperthyroidism in patients intolerant of orally and rectally administered thionamides. METHODS: Five hundred milligrams of methimazole USP powder was reconstituted with pH-neutral 0.9% sodium chloride solution to a final volume of 50 mL using aseptic technique, then filtered through a 0.22-microm filter. MMI injection was administered as a slow intravenous push over 2 minutes and followed by a saline flush. CASES: A 76-year-old man, intolerant of oral and rectal medications because of an ileus and intractable diarrhea, who developed worsening thyrotoxicosis after an emergent spinal cord decompression, and a 42-year-old man with chronic liver disease and hyperthyroidism, requiring emergent exploratory laparotomy and maintenance of complete bowel rest because of persistent gastrointestinal bleeding were rendered euthyroid using intravenous MMI. CONCLUSION: Two cases of hyperthyroidism successfully treated with a preparation of intravenous MMI are described.

Adult↗

PubMed2006

Thyroid medications during pregnancy.

Euthyroid women experience dramatic changes in their thyroid physiology in order to accommodate the presence of placental and fetal tissues. These adaptations to the pregnant state make it crucial to develop reliable trimester-specific intervals for thyroid parameters. Use of non-pregnant reference intervals could lead to erroneous assessment of thyroid status in this rapidly changing hormonal environment. Only with a full appreciation of physiologic changes in thyroid parameters during a euthyroid pregnancy, can thyroid dysfunction be appropriately diagnosed and managed. Iodine sufficiency during pregnancy can be achieved with supplementation using a multivitamin. Both hypothyroidism and hyperthyroidism should be diagnosed using the appropriate reference intervals for pregnancy. Hypothyroid women are best treated with a specific brand of levothyroxine. Hypothyroidism should ideally be treated prior to conception. If newly recognized during pregnancy, it should be fully treated as early as possible. Frequent monitoring of thyroid status is essential as many women demonstrate an increased requirement for thyroid hormone during the first trimester. Although mild hyperthyroidism may be well tolerated during pregnancy, overt hyperthyroidism requires treatment. Thionamides are the mainstay of therapy. Following their initiation, close monitoring is required to avoid maternal and fetal hypothyroidism. There are occasional circumstances when other medical therapy or surgical therapy may be employed for hyperthyroidism. Thyroidectomy is generally safe in the second trimester in an appropriately prepared woman. There is limited data about the role and safety of oral contrast agents, iodine, amiodarone, and perchlorate. Radioiodine therapy is contradicted during pregnancy.

Antithyroid Agents↗

PubMed2005

The measurement of free thyroxine by isotope dilution tandem mass spectrometry.

BACKGROUND: Most clinical chemistry laboratories measure free thyroxine (FT4) by an analogue (direct) method. Nevertheless, the validity of analogue FT4 immunoassays has been questioned and patient's results using this approach frequently do not fit in with the clinical presentation. Because of these problems we routinely send out all direct free T4's that are < 2.5th percentile and many that are > 97.5th percentile for measurement by equilibrium dialysis, the gold standard method. In approximately half of these cases, the FT4 by equilibrium dialysis was normal. We developed a rapid, reliable free T4 method employing isotope dilution tandem mass spectrometry and compared our results with both the analogue (direct) free T4 and equilibrium dialysis procedures. METHODS: An API-4000 tandem mass spectrometer (Sciex, Toronto, Canada) equipped with TurboIonSpray and Agilent HPLC system was used employing isotope dilution with deuterium labeled internal standard (IS=l-thyroxine-d2). Serum was filtered through the Centrifree YM-30 ultrafiltration device by centrifugation, IS added to the ultrafiltrate, and 400 microL injected onto a C-18 column. After washing, the switch valve is activated and a methanol gradient allows for elution of both T4 and the IS into the LC/MS/MS system. Quantitation was by MRM analysis in the negative mode. Equilibrium dialysis was performed by the Nichols method and analogue free T4 results were obtained on the Dade Dimension RxL. RESULTS: The within-day and between-day CV's were < 7.1% at all concentrations tested. The results correlated well with equilibrium dialysis (Eq Dial=0.971 MS+0.041, n=68, Syx=1.381, r=0.954). A poor correlation was found with the analogue (direct) free T4 method (IA=0.326 MS+6.27, n=154, Syx=1.96, r=0.459). CONCLUSIONS: Samples can be processed in batches of 30. The free T4 tandem MS method has a rapid turn-around-time vs the equilibrium dialysis procedure, with a chromatographic run time of 8 min per sample.

Chromatography, Liquid↗

PubMed2005

Cushing's syndrome during pregnancy: personal experience and review of the literature.

Cushing's syndrome (CS) occurs rarely during pregnancy. We investigated and treated four patients with pituitary-dependent Cushing's syndrome during pregnancy over a 15-yr period at the National Institutes of Health. Except for preservation of menses before conception, our patients presented with typical clinical features, increased urinary free cortisol, and loss of diurnal variation of cortisol. The diagnosis was facilitated, without complications, by the use of CRH testing and inferior petrosal sinus sampling in three women. Transsphenoidal pituitary surgery achieved remission in three women, but there were two fetal/neonatal deaths. This experience and review of 136 previous reports suggest that: 1) urinary free cortisol in CS patients overlaps the normal pregnant range; 2) ACTH levels are not suppressed in adrenal causes of CS, which may be identified by the 8-mg dexamethasone test; 3) inferior petrosal sinus sampling and transsphenoidal pituitary surgery, the optimal diagnostic test and treatment for nonpregnant patients with pituitary-dependent Cushing's syndrome, can safely facilitate the management of pregnant patients; and 4) surgery may achieve remission during pregnancy, but the prognosis for the fetus remains guarded. It is likely that earlier recognition and treatment would improve outcome. There is a need for development of criteria for interpretation of diagnostic tests and increased consideration of CS in pregnancy.

Adrenocorticotropic Hormone↗

PubMed2005

Radioiodine therapy for thyroid cancer and hyperthyroidism in patients with end-stage renal disease on hemodialysis.

Treatment with radioactive iodine ((131)I) may be necessary for thyroid cancer or for hyperthyroidism in patients with end-stage renal disease who require hemodialysis. Because (131)I is cleared mainly by the kidneys in patients with normal renal function, many issues arise in patients who require (131)I treatment but who are on hemodialysis. This paper presents a case report of a patient on dialysis who required treatment with (131)I for thyroid cancer. We describe a mathematical model, which suggests that the treatment dose of (131)I for a patient with thyroid cancer on hemodialysis would be approximately 13%-28% of a typical empiric dose of (131)I for a patient with normal renal function. Also, we present a comprehensive review and discussion of the literature on patients who are receiving hemodialysis who were treated with (131)I for either thyroid cancer or hyperthyroidism. Using a multidisciplinary approach and special precautions, (131)I therapy can be administered safely and effectively for patients with thyroid cancer or hyperthyroidism who are receiving hemodialysis.

Adult↗

PubMed2005

Ectopic intratracheal thyroid: an illustrative case report and literature review.

A 19-year-old woman was treated with bronchodilators for new-onset dyspnea with exercise. Her symptoms progressively worsened, culminating 4 months later in acute shortness of breath at rest. Flow-volume loops suggested a fixed obstruction and a computed tomography scan of the neck revealed a large subglottic mass. The patient underwent emergent tracheostomy and laryngoscopy and a near-obstructing intratracheal mass was found. Biopsy showed ectopic thyroid tissue. Magnetic resonance imaging of the neck showed a 1.4-cm tracheal lesion and a normally located thyroid gland. The intratracheal mass was resected endoscopically. Pathology revealed hyperplastic ectopic thyroid tissue. The patient has been maintained on thyroid hormone suppression therapy for 2 years without growth of the residual intratracheal thyroid tissue. She recently underwent a surgical palate expansion. We present this case, along with a literature review of ectopic intratracheal thyroid, its epidemiology, possible etiologies, genetic underpinnings, presentation, and treatment. The co-occurrence of an ectopic thyroid, a functioning orthotopic gland, and a high arched palate is also discussed.

Adult↗

PubMed2005

Transient Graves' hyperthyroidism during pregnancy in a patient with Hashimoto's hypothyroidism.

The course and severity of autoimmune thyroid disease are altered during pregnancy and in the postpartum period. The thyroidal response to a fluctuating immune status, combined with changes in thyroid economy during pregnancy, may result in a need to adjust the treatment regimen for thyroid disease during pregnancy. Patients with Hashimoto's hypothyroidism on thyroid hormone replacement are frequently observed to have an increased requirement for levothyroxine early in pregnancy, although this is not a universal finding. Hashimoto's hypothyroidism does not typically remit during pregnancy, although further progression of thyroiditis may be seen in the postpartum period. Graves' disease usually improves during pregnancy and flares after delivery, again necessitating monitoring of thyroid status and possible adjustments in thionamide therapy. However, spontaneous transformation from Hashimoto's hypothyroidism to Graves' disease during pregnancy is rare. We report a case of transient Graves' hyperthyroidism during the late second trimester in a patient on levothyroxine replacement for Hashimoto's hypothyroidism. This resulted in a need to discontinue the patient's thyroid hormone entirely to avoid exacerbation of her hyperthyroidism. This interesting case is presented, along with a discussion of how the expression of autoimmune thyroid disease may be altered during pregnancy.

Adult↗

PubMedDate not supplied

Atypical presentation of a patient with both kallmann syndrome and a craniopharyngioma: case report and literature review.

OBJECTIVE: To describe an unusual presentation of a patient with Kallmann syndrome, without the typical eunuchoid features, who had additional hormonal abnormalities caused by a craniopharyngioma. METHODS: This patient's clinical features, endocrine evaluation, and treatment are described, and the literature regarding Kallmann syndrome is reviewed. The expected phenotype of Kallmann syndrome is contrasted with this case presentation. A literature search was also performed to determine whether the combination of craniopharyngioma and Kallmann syndrome had been described previously. RESULTS: A 23-year-old man had a suprasellar tumor in conjunction with hypogonadotropic hypogonadism and growth hormone deficiency. Subsequently, he was also noted to have anosmia, a cleft palate, and bilateral olfactory bulb hypoplasia. His height was less than his calculated midparental height and exceeded his arm span. Defective neuronal migration in Kallmann syndrome is caused by absence of adhesion proteins needed for cellular, neuronal, and axonal guidance. This results in failure of olfactory and gonadotropin-releasing hormone neurons to complete normal migration. Defective migration can also cause midline craniofacial abnormalities, renal agenesis, and cardiovascular defects. Arachnoid cysts have been reported in two patients with Kallmann syndrome, although whether a migration defect underlies their occurrence is speculative. No prior reports of craniopharyngioma in a patient with Kallmann syndrome could be identified. CONCLUSION: It is postulated that although this patient had Kallmann syndrome, he did not present with a eunuchoid body habitus because of concomitant growth hormone deficiency caused by his craniopharyngioma. Although midline craniofacial abnormalities have been seen in patients with Kallmann syndrome, this patient's craniopharyngioma seems more likely to be coincidental, rather than being one of the developmental anomalies that are part of the spectrum of this syndrome.

Adult↗