John S. Bevan

Treatment of macroprolactinoma with cabergoline: a study of 85 patients

OBJECTIVE Cabergoline is now established as an effective and well‐tolerated treatment for prolactinoma. However, there are relatively few published data on the treatment of macro‐, as opposed to micro‐, prolactinoma. We have therefore reviewed the efficacy and safety of cabergoline in the treatment of patients with prolactin‐secreting macroadenomas treated on a compassionate basis.

Radioiodine therapy (RAI) for Graves’ disease (GD) and the effect on ophthalmopathy: a systematic review

Background  An association between radioiodine therapy (RAI) for Graves’ disease (GD) and the development or worsening of Graves’ ophthalmopathy (GO) is widely quoted but there has been no systematic review of the evidence.

Tumor Shrinkage With Lanreotide Autogel 120 mg as Primary Therapy in Acromegaly: Results of a Prospective Multicenter Clinical Trial

Context: Methodological shortcomings often compromise investigations into the effects of primary somatostatin-analog treatment on tumor size in acromegaly. There are also limited data for the long-acting lanreotide formulation. Objective: The aim of the study was to better characterize the effects of primary lanreotide Autogel treatment on tumor size in patients with GH-secreting macroadenomas. Design: PRIMARYS was a 48-week, multicenter, open-label, single-arm study. Setting: The study was conducted at specialist endocrine centers. Patients: Treatment-naïve acromegalic patients with GH-secreting macroadenomas participated in the study. Intervention: Lanreotide Autogel 120 mg was administered sc every 28 days (without dose titration). Outcome Measures: The primary endpoint was the proportion of patients with clinically significant (≥20%) tumor volume reduction (TVR) at week 48/last post-baseline value available using central assessments from three readers. The null hypothesis (H0) for the primary endpoint was that the proportion with TVR was ≤55%. Secondary endpoints included: TVR at other time points, GH and IGF-1, acromegalic symptoms, quality of life (QoL), and safety. Results: Sixty-four of 90 (71.1%) patients completed the study. Clinically significant TVR at 48 weeks/last post-baseline value available was achieved by 62.9% (95% confidence interval, 52.0, 72.9) of 89 patients in the primary analysis (intention-to-treat population; H0 not rejected) and 71.9–75.3% in sensitivity (n = 89) and secondary analyses (n = 63) (H0 rejected). At 12 weeks, 54.1% had clinically significant TVR. Early and sustained improvements also occurred in GH and IGF-1, acromegalic symptoms, and QoL. No patients withdrew due to gastrointestinal intolerance. Conclusions: Primary treatment with lanreotide Autogel, administered at 120 mg (highest available dose) without dose titration, in patients with GH-secreting macroadenomas provides early and sustained reductions in tumor volume, GH and IGF-1, and acromegalic symptoms, and improves QoL.

Heterogeneous Genetic Background of the Association of Pheochromocytoma/Paraganglioma and Pituitary Adenoma: Results From a Large Patient Cohort

Context: Pituitary adenomas and pheochromocytomas/paragangliomas (pheo/PGL) can occur in the same patient or in the same family. Coexistence of the two diseases could be due to either a common pathogenic mechanism or a coincidence. Objective: The objective of the investigation was to study the possible coexistence of pituitary adenoma and pheo/PGL. Design: Thirty-nine cases of sporadic or familial pheo/PGL and pituitary adenomas were investigated. Known pheo/PGL genes (SDHA-D, SDHAF2, RET, VHL, TMEM127, MAX, FH) and pituitary adenoma genes (MEN1, AIP, CDKN1B) were sequenced using next generation or Sanger sequencing. Loss of heterozygosity study and pathological studies were performed on the available tumor samples. Setting: The study was conducted at university hospitals. Patients: Thirty-nine patients with sporadic of familial pituitary adenoma and pheo/PGL participated in the study. Outcome: Outcomes included genetic screening and clinical characteristics. Results: Eleven germline mutations (five SDHB, one SDHC, one SDHD, two VHL, and two MEN1) and four variants of unknown significance (two SDHA, one SDHB, and one SDHAF2) were identified in the studied genes in our patient cohort. Tumor tissue analysis identified LOH at the SDHB locus in three pituitary adenomas and loss of heterozygosity at the MEN1 locus in two pheochromocytomas. All the pituitary adenomas of patients affected by SDHX alterations have a unique histological feature not previously described in this context. Conclusions: Mutations in the genes known to cause pheo/PGL can rarely be associated with pituitary adenomas, whereas mutation in a gene predisposing to pituitary adenomas (MEN1) can be associated with pheo/PGL. Our findings suggest that genetic testing should be considered in all patients or families with the constellation of pheo/PGL and a pituitary adenoma.

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.

Cushing’s Syndrome during Pregnancy: Curative Adrenalectomy at 31 Weeks Gestation

A case of Cushings syndrome due to benign adrenal adenoma (Ad) arising in pregnancy is described. Accurate tumour localisation with magnetic resonance imaging facilitated definitive surgical intervention. Curative adrenalectomy was performed via a posterior approach in the third trimester with subsequent uncomplicated delivery of a healthy infant.

Comparison of monthly intramuscular injections of Sandostatin LAR with multiple subcutaneous injections of octreotide in the treatment of acromegaly; effects on growth hormone and other markers of growth hormone secretion.

To compare the effects of monthly intramuscular injections of a long acting preparation of octreotide, Sandostatin LAR, with multiple daily subcutaneous injections of octreotide and to study the interrelationships between mean 24 h growth hormone profile, serum total and free IGF‐1 levels, 24 h urinary growth hormone levels and serum IGFBP‐3.

Giant bilateral myelolipomas in a man with congenital adrenal hyperplasia.

A 34-yr-old man presented with abdominal swelling and discomfort. Congenital adrenal hyperplasia had been diagnosed as a neonate (homozygous for g.655A/C G point mutation in CYP21A2). During adulthood, he was treated with dexamethasone 0.25 mg twice daily and fludrocortisone 0.1 mg once daily. He defaulted from adult clinic follow-up and had not collected his dexamethasone prescriptions for 1 yr. He suffered from epilepsy managed by a variety of anticonvulsants, including enzyme-inducing drugs. He was pigmented and had a 20-cm mass palpable in the left abdomen that extended across the midline. An ill-defined smaller mass was palpable deep in the right abdomen. Serum hormone levels before and after morning steroid administration showedACTHsuppressing from407 to12 ng/liter, 17 -hydroxyprogesterone falling from 605 to 192 nmol/liter, testosterone falling from 34 to 11.2 nmol/ liter, and cortisol ranged between 80 and 130 nmol/liter; basal LH and FSH were undetectable. The patient underwent bilateral adrenalectomy, and pathology confirmed bilateral giant myelolipomas (Fig. 1)—the left weighing 5.8 kg (230 110 190 mm) and the right weighing 780 g (150 130 68 mm). On postoperative replacement with hydrocortisone 20 10 mg and fludrocortisone 0.1 mg, 17 -hydroxyprogesterone was 6 nmol/liter, testosterone was 17.6 nmol/liter, LH was 14 U/liter, and FSH was 17 U/liter. This suggested reactivation of the pituitary-gonadal axis, previously suppressed by high levels of adrenal-derived androgens. Giant bilateral adrenal myelolipomas are rare (1–5); our patient’s left-side tumor is among the largest reported (4, 5). Chronic ACTH hyperstimulation is thought to be involved in pathogenesis and in this case resulted from poor steroid compliance and likely enhanced corticosteroid metabolism due to concomitant treatment with enzyme-inducing anticonvulsants.

An audit of the diagnostic usefulness of PRL and TSH responses to domperidone and high resolution magnetic resonance imaging of the pituitary in the evaluation of hyperprolactinaemia

BACKGROUND AND OBJECTIVE The usefulness of dynamic tests of PRL release in determining underlying pathology in hyperprolactinaemic patients is not well recognized by endocrinologists, only 15% of whom routinely perform such tests. High resolution pituitary magnetic resonance imaging (MRI) has become more widely available during the past 5 years and is now generally regarded as the pituitary imaging method of choice. Since few prolactinoma patients are now submitted to surgery, it is important to ascertain the usefulness of these techniques in suggesting a pathological diagnosis.

Should all patients with acromegaly receive somatostatin analogue therapy before surgery and, if so, for how long?

Current guidelines do not recommend the routine use of somatostatin analogue pretreatment prior to surgery in patients with growth hormone‐secreting pituitary tumours. In theory, presurgical use of somatostatin analogues should improve metabolic control and reduce soft tissue swelling, leading to improved anaesthetic outcomes. Shrinkage of tumours prior to surgery might also improve surgical remission rates. Hence, this article addresses the question: Should all patients with acromegaly receive a somatostatin analogue prior to surgery? Clinical trials published before December 2013 were reviewed, although literature in this area remains relatively deficient. We conclude: (i) On the basis of limited data available, somatostatin analogue pretreatment does not improve anaesthetic or immediate postoperative outcomes (i.e. hospital stay, rates of surgical complications and postoperative pituitary dysfunction). (ii) Somatostatin analogues should be considered in all patients with growth hormone‐secreting macroadenomas, including invasive macroadenomas, when the overall surgical remission rate for macroadenomas at the treating centre is below 50%. Four recent RCTs have demonstrated increased rates of surgical remission using such an approach. (iii) When deemed appropriate, patients should be treated with somatostatin analogues for at least 3 months before surgery; there is currently no evidence that treatment beyond 6 months provides any additional benefit. Patients with minimally invasive macroadenomas are those most likely to benefit in terms of improved surgical remission.