The PRolaCT studies - a study protocol for a combined randomised clinical trial and observational cohort study design in prolactinoma.

BACKGROUND: First-line treatment for prolactinomas is a medical treatment with dopamine agonists (DAs), which effectively control hyperprolactinaemia in most patients, although post-withdrawal remission rates are approximately 34%. Therefore, many patients require prolonged DA treatment, while side effects negatively impact health-related quality of life (HRQoL). Endoscopic transsphenoidal resection is reserved for patients with severe side effects, or with DA-resistant prolactinoma. Surgery has a good safety profile and high probability of remission and may thus deserve a more prominent place in prolactinoma treatment. The hypothesis for this study is that early or upfront surgical resection is superior to DA treatment both in terms of HRQoL and remission rate in patients with a non-invasive prolactinoma of limited size. METHODS: We present a combined randomised clinical trial and observational cohort study design, which comprises three unblinded randomised controlled trials (RCTs; PRolaCT-1, PRolaCT-2, PRolaCT-3), and an observational study arm (PRolaCT-O) that compare neurosurgical counselling, and potential subsequent endoscopic transsphenoidal adenoma resection, with current standard care. Patients with a non-invasive prolactinoma (< 25 mm) will be eligible for one of three RCTs based on the duration of pre-treatment with DAs: PRolaCT-1: newly diagnosed, treatment-naïve patients; PRolaCT-2: patients with limited duration of DA treatment (4-6 months); and PRolaCT-3: patients with persisting prolactinoma after DA treatment for > 2 years. PRolaCT-O will include patients who decline randomisation, due to e.g. a clear treatment preference. Primary outcomes are disease remission after 36 months and HRQoL after 12 months. DISCUSSION: Early or upfront surgical resection for patients with a limited-sized prolactinoma may be a reasonable alternative to the current standard practice of DA treatment, which we will investigate in three RCTs and an observational cohort study. Within the three RCTs, patients will be randomised between neurosurgical counselling and standard care. The observational study arm will recruit patients who refuse randomisation and have a pronounced treatment preference. PRolaCT will collect randomised and observational data, which may facilitate a more individually tailored practice of evidence-based medicine. TRIAL REGISTRATION: US National Library of Medicine registry (ClinicalTrials.gov) NCT04107480 . Registered on 27 September 2019, registered retrospectively (by 2 months).

A germline c.1546dupC MEN1 mutation in an MEN1 family: A case report.

RATIONALE: Multiple endocrine neoplasia type 1 (MEN1) is a rare tumor syndrome with an autosomal dominant inheritance, and genetic testing for MEN1 gene is important for both affected individuals and their relatives. We present a 2-person family affected by a germline c.1546dupC MEN1 mutation, and one of them had a full-spectrum of MEN-related endocrine tumors. PATIENT CONCERNS: A female patient aged 32 years presented with jejunal ulcer perforation due to gastrinoma. DIAGNOSES: We conducted genetic analysis and extensive biochemical/radiological evaluation for detecting other endocrine tumors. Multiple pancreatic neuroendocrine tumors (NETs), prolactinoma and primary hyperparathyroidism were diagnosed, and a frame-shift mutation, NM_130799.1:c.1546dupC (p.Arg516Profs∗15), was detected. One daughter of the proband, aged 12 years, had the same mutation for MEN1. INTERVENTION: She underwent pancreatic surgery for pancreatic NETs and total parathyroidectomy for primary hyperparathyroidism. OUTCOMES: After pancreatic surgery, long-term symptoms of epigastric soreness, acid belching, sweating, and palpitation in fasting were improved. Hypercalcemia was improved after parathyroidectomy and she was supplemented with oral calcium and vitamin D. Her daughter showed normal biochemical surveillance until 15 years of age. LESSONS: We report 2 people in a family affected by MEN1 with the heterozygous germline c.1546dupC mutation, a variant that should be surveilled for early development of full-blown MEN1-associated endocrine tumors.

Pituitary Microadenoma Treated with Individualized Homeopathic Medicine: A Case Report.

BACKGROUND: Pituitary adenomas are common benign tumors of the pituitary gland with an overall estimated prevalence of 16.7%. As per the revised World Health Organization (WHO) classification, these tumors are identified by their histological subtypes and are designated by their pituitary cell lineage instead of the hormone they produce. The lactotroph adenoma is the most common subtype of hormone-producing pituitary adenoma. Surgery is the mainstay of treatment, but complications are encountered. So far, there is no reported study evaluating individualized homeopathic intervention in pituitary adenoma in peer-reviewed journals. METHODS: This case study describes a case of functional lactotroph microadenoma with history of failed surgical treatment and heavy intrasellar hemorrhage occurring during the surgery. Phosphorus was prescribed as an individualized homeopathic medicine on the basis of symptoms-hemorrhagic complication during surgical procedure and aggravation of headache thereafter. RESULTS: There was a marked subjective improvement along with complete tumor regression, as evidenced by repeat magnetic resonance imaging scans. The Modified Naranjo Criteria total score was +10 out of a possible +13, providing some evidence to attribute the clinical outcome with the homeopathic intervention. CONCLUSION: This case study reconfirms the association between increased frequency of headaches and pituitary hemorrhage among cases of lactotroph adenoma. It also suggests that individualized homeopathic treatment may be helpful in pituitary adenomas with increased risk of complications such as intrasellar hemorrhage.

Spontaneous shrinking of a macroprolactinoma.

The case of a male patient with a macroprolactinoma is presented. Within a follow up period of six months the tumor had spontaneously shrunken without any therapy. The causes of this phenomenon are discussed in the following paper.

Evolucion de prolactinomas en adolescentes / The course of prolactinomas in adolescents

Se presentan los resultados del tratamiento y seguimiento a mediano y largo plazo en 13 pacientes (8 niñas y 5 varones) de 14.2 a 20 años (x:16,5) portadores de prolactinoma. En el momento de la consulta los signos clínicos, más frecuentes fueron: cefaleas, detención o retraso de la pubertad, galactorrea y alteraciones visuales. La evaluación pretratamiento mostró respsuestas variables y discordantes de LH y FSH al ensayo de LH-RH, mientras que la prueba de TRH (TSH) resultó normal en 8/9 casos (una joven mostró un hipotiroidismo primario asociado). Los niveles de prolactina (PRL) basales estaban elevados en todos los casos entre 77 y 1150 ng/ml (x ñ SD : 378 ñ 285), sin incremento luego del TRH (x : 25%). En 8 casos, la cirugía constituyó el tratamiento inicial; 7 de ellos persistieron hiperprolactinémicos y requirieron bromocriptina (BEC) postquirúrgica. Cinco enfermos recibieron BEC como tratamiento primario; la TC mostró desaparición o importante reducción tumoral en 4 y ausencia de modificaciones en 1 niña por lo que se indicó cirugía secundariamente. La evolución pudo seguirse en 11 pacientes entre 2 y 12 años. De los operados inicialmente, 1 recuperó espontáneamente la función gonadal y 5 casos requirieron tratamiento complementario. De los 5 casos tratados primariamente con BEC, una recuperó ciclos espontáneamente logrado embarazo a los 10 meses, una completó el desarrollo puberal y presenta sangrados periódicos, una requirió tratamiento complementario con progesterona y el varón recuperó la función gonadal. La niña que fue secundariamente operada persiste normoprolactinémia sin recuperar sus ciclos. Concluimos que: 1) la PRL basal, junto con la evaluación radiológica, constituyen los elementos fundamentales en el diagnóstico de prolactinoma; 2) las evidencias clínicas y radiológicas abonarían en favor de una mayor rapidez evolutiva en los varones; 3) la BEC constituye un recurso valioso en el tratamiento primario o complementario de los prolactinomas en pacientes infantojuveniles

Evolucion de prolactinomas en adolescentes / The course of prolactinomas in adolescents

Se presentan los resultados del tratamiento y seguimiento a mediano y largo plazo en 13 pacientes (8 niñas y 5 varones) de 14.2 a 20 años (x:16,5) portadores de prolactinoma. En el momento de la consulta los signos clínicos, más frecuentes fueron: cefaleas, detención o retraso de la pubertad, galactorrea y alteraciones visuales. La evaluación pretratamiento mostró respsuestas variables y discordantes de LH y FSH al ensayo de LH-RH, mientras que la prueba de TRH (TSH) resultó normal en 8/9 casos (una joven mostró un hipotiroidismo primario asociado). Los niveles de prolactina (PRL) basales estaban elevados en todos los casos entre 77 y 1150 ng/ml (x ñ SD : 378 ñ 285), sin incremento luego del TRH (x : 25%). En 8 casos, la cirugía constituyó el tratamiento inicial; 7 de ellos persistieron hiperprolactinémicos y requirieron bromocriptina (BEC) postquirúrgica. Cinco enfermos recibieron BEC como tratamiento primario; la TC mostró desaparición o importante reducción tumoral en 4 y ausencia de modificaciones en 1 niña por lo que se indicó cirugía secundariamente. La evolución pudo seguirse en 11 pacientes entre 2 y 12 años. De los operados inicialmente, 1 recuperó espontáneamente la función gonadal y 5 casos requirieron tratamiento complementario. De los 5 casos tratados primariamente con BEC, una recuperó ciclos espontáneamente logrado embarazo a los 10 meses, una completó el desarrollo puberal y presenta sangrados periódicos, una requirió tratamiento complementario con progesterona y el varón recuperó la función gonadal. La niña que fue secundariamente operada persiste normoprolactinémia sin recuperar sus ciclos. Concluimos que: 1) la PRL basal, junto con la evaluación radiológica, constituyen los elementos fundamentales en el diagnóstico de prolactinoma; 2) las evidencias clínicas y radiológicas abonarían en favor de una mayor rapidez evolutiva en los varones; 3) la BEC constituye un recurso valioso en el tratamiento primario o complementario de los prolactinomas en pacientes infantojuveniles (AU)