Trevor Howlett

An assessment of optimal hydrocortisone replacement therapy

OBJECTIVE To assess the management of hydrocortisone replacement therapy in one institution, and derive recommendations for optimum starting and maintenance replacement therapy with hydrocortisone.

AIP Mutation in Pituitary Adenomas in the 18th Century and Today

Gigantism results when a growth hormone-secreting pituitary adenoma is present before epiphyseal fusion. In 1909, when Harvey Cushing examined the skeleton of an Irish patient who lived from 1761 to 1783, he noted an enlarged pituitary fossa. We extracted DNA from the patients teeth and identified a germline mutation in the aryl hydrocarbon-interacting protein gene (AIP). Four contemporary Northern Irish families who presented with gigantism, acromegaly, or prolactinoma have the same mutation and haplotype associated with the mutated gene. Using coalescent theory, we infer that these persons share a common ancestor who lived about 57 to 66 generations earlier.

Diabetes and cardiovascular events in women with polycystic ovary syndrome: a 20‐year retrospective cohort study

Women with polycystic ovary syndrome (PCOS) are potentially at increased risk of cardiovascular (CV) diseases due to well‐established risk factors, including insulin resistance, obesity and type 2 diabetes mellitus (T2DM). However, data showing excess CV events in this population are still lacking. We investigated the incidence and prevalence of CV events in a cohort of women with PCOS.

Cabergoline treatment of acromegaly: a preliminary dose finding study

Studies of the dopamine agonist cabergoline in the treatment of hyperprolactinaemia have shown it to be a potent, long‐acting and well‐tolerated. The older dopamine agonist, bromocriptine, has traditionally had a place in the medical management of acromegaly, but poor patient tolerance of the high doses required, the need for multiple daily administration and incomplete biochemical responses have limited its role. We therefore sought to investigate the effect of cabergoline on growth hormone (GH) secretion in acromegaly and to define the most appropriate dose for suppression of GH

Home administration of lanreotide Autogel ® by patients with acromegaly, or their partners, is safe and effective

Objective  The introduction of ready‐to‐use lanreotide Autogel® has presented the possibility of patients receiving their acromegaly treatment at home. The objective of this study was to assess the ability of patients (or their partners) to administer repeat, unsupervised, injections of lanreotide Autogel without compromising efficacy or safety.

Preliminary observations using endocrine markers of pituitary venous dilution during bilateral simultaneous inferior petrosal sinus catheterization in Cushing's syndrome: is combined CRF and TRH stimulation of value?

OBJECTIVE We determined whether the measurement of hormones in pituitary blood permits correction for dilution by non‐pituitary blood during bilateral simultaneous inferior petrosal sinus blood sampling in Cushings syndrome. DESIGN Bilateral simultaneous inferior petrosal sinus blood sampling was performed after combined hCRF and TRH stimulation. Peak ACTH concentrations were corrected for the TSH and PRL inter‐sinus ratio, assuming uniform secretion of both hormones into each inferior petrosal sinus.

A Cross-Sectional Study of the Prevalence of Cardiac Valvular Abnormalities in Hyperprolactinemic Patients Treated With Ergot-Derived Dopamine Agonists

CONTEXT Concern exists in the literature that the long-term use of ergot-derived dopamine agonist drugs for the treatment of hyperprolactinemia may be associated with clinically significant valvular heart disease. OBJECTIVE The aim of the study was to determine the prevalence of valvular heart abnormalities in patients taking dopamine agonists as treatment for lactotrope pituitary tumors and to explore any associations with the cumulative dose of drug used. DESIGN A cross-sectional echocardiographic study was performed in a large group of patients who were receiving dopamine agonist therapy for hyperprolactinemia. Studies were performed in accordance with the British Society of Echocardiography minimum dataset for a standard adult transthoracic echocardiogram. Poisson regression was used to calculate relative risks according to quartiles of dopamine agonist cumulative dose using the lowest cumulative dose quartile as the reference group. SETTING Twenty-eight centers of secondary/tertiary endocrine care across the United Kingdom participated in the study. RESULTS Data from 747 patients (251 males; median age, 42 y; interquartile range [IQR], 34-52 y) were collected. A total of 601 patients had taken cabergoline alone; 36 had been treated with bromocriptine alone; and 110 had received both drugs at some stage. The median cumulative dose for cabergoline was 152 mg (IQR, 50-348 mg), and for bromocriptine it was 7815 mg (IQR, 1764-20 477 mg). A total of 28 cases of moderate valvular stenosis or regurgitation were observed in 24 (3.2%) patients. No associations were observed between cumulative doses of dopamine agonist used and the age-corrected prevalence of any valvular abnormality. CONCLUSION This large UK cross-sectional study does not support a clinically concerning association between the use of dopamine agonists for the treatment of hyperprolactinemia and cardiac valvulopathy.

Diagnosis and treatment of hypothyroidism in TSH deficiency compared to primary thyroid disease: pituitary patients are at risk of under‐replacement with levothyroxine

Objective  Achieving optimal thyroid hormone replacement is more difficult in TSH deficiency compared to primary hypothyroidism because of the inability to be guided by serum TSH levels. A combination of clinical symptoms and free thyroxine levels (fT4) are typically used to make a diagnosis and monitor replacement. We investigated the diagnosis of TSH deficiency in patients with pituitary disease and the adequacy of levothyroxine replacement compared with primary thyroid disease.

How reliably can autoimmune hypophysitis be diagnosed without pituitary biopsy.

Autoimmune hypophysitis is a rare chronic inflammatory condition of the pituitary gland which typically presents with hypopituitarism and a pituitary mass. Cases involving anterior pituitary alone (65%) are six times more common in women, typically presenting during pregnancy or postpartum (57%). Anterior and posterior pituitary involvement (25%) are twice as common in women, and neurohypophysis alone (10%) occurs equally in both sexes. It has a prevalence of around 5 per million, an annual incidence of 1 in 7 to 9 million and in our experience represents the known or suspected cause of 0·5% of cases of hypopituitarism, <1% of pituitary masses and 2% of nonfunctioning macro lesions presenting to an endocrine clinic. However, ‘missed’ cases of autoimmune hypophysitis may be the aetiology of some other unexplained cases of hypopituitarism. Clinically, headache and visual disturbance are common. Anterior hypopituitarism shows a characteristic but atypical pattern of deficiency of ACTH followed by TSH, gonadotrophins and prolactin deficiency or hyperprolactinaemia. Eighteen percent of cases have evidence of another autoimmune condition. On magnetic resonance imaging (MRI), autoimmune hypophysitis is typically symmetrical and homogeneous with thickened but undisplaced stalk in contrast to typical findings with pituitary tumours. Ultimately, the histological diagnosis of autoimmune hypophysitis can only be confirmed by surgery but a presumptive diagnosis can often be made on the basis of a combination of context and clinical features, and pituitary biopsy is not always clinically necessary for effective clinical management of the patient.

MANAGEMENT OF PITUITARY INCIDENTALOMAS: A Survey of British and American Endocrinologists

The results of a survey of endocrinologists concerning their approaches to the evaluation of a patient with an incidentally discovered pituitary mass are presented in this article. The practices of British and American endocrinologists are compared. The wide variation in diagnostic approaches to the practice of ordering tests in the United Kingdom and the United States highlights the need for research and debate regarding the most appropriate management of patients with such findings.