Dynamic testing after pituitary surgery: is follow-up re-testing useful?

The insulin tolerance test (ITT) is considered the gold standard for assessment of GH and ACTH reserve in patients with pituitary disease following pituitary surgery and is usually performed after 6–12 weeks. However, abnormal axes may not be completely recovered by then. The aim of this study was to evaluate dynamic testing 3 and 12 months after transsphenoidal pituitary surgery.Design and patientsSerial dynamic testing was performed in 36 patients (13 women, age 18–78) at 3 and 12 months after transsphenoidal surgery.ResultsCompared with 3-month results, median GH peak levels during ITT after 12 months increased by 38% (P<0.05). In patients initially classified as GH deficiency (GHD), median GH peak increased after 12 months by 23% (P<0.05). At 3 and 12 months, 36% (13/36) and 47% (17/36) were GH sufficient respectively. Median cortisol peak levels after 12 months increased by 17% (P<0.01) compared with 3-month ITT. In ACTH-insufficient (AI) patients, peak cortisol levels increased significantly by 12% (P<0.05) at 12 months, and in ACTH-sufficient patients, peak cortisol levels increased significantly by 13% (P<0.05). At 12 months, there was recovery from AI in 11% of the patients, and recovery from GHD in 11% of patients.ConclusionsSerial dynamic testing results in a change in classification by ITT results in a relevant proportion of patients. Dynamic testing should be repeated during follow-up.

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P34 Characteristics, diagnosis and management of Cushing’s disease - A systematic review and meta-analysis

BJS Open ◽

10.1093/bjsopen/zrab032.033 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

Author(s):

Chan Hee Koh ◽

Danyal Z Khan ◽

Ronneil Digpal ◽

Hugo Layard Horsfall ◽

Hani J Marcus ◽

...

Keyword(s):

Clinical Practice ◽

Cushing’S Disease ◽

Meta Analysis ◽

A Priori ◽

Pituitary Surgery ◽

Serum Cortisol ◽

Cushing's Disease ◽

Diagnosis And Management ◽

Over Time

Abstract Introduction The clinical practice and research in the diagnosis and management of Cushing’s disease remains heterogeneous and challenging to this day. We sought to establish the characteristics of Cushing’s disease, and the trends in diagnosis, management and reporting in this field. Methods Searches of PubMed and Embase were conducted. Study protocol was registered a-priori. Random-effects analyses were conducted to establish numerical estimates. Results Our screening returned 159 papers. The average age of adult patients with Cushing’s disease was 39.3, and 13.6 for children. The male:female ratio was 1:3. 8% of patients had undergone previous transsphenoidal resection. The ratio of macroadenomas: microadenomas:imaging-undetectable adenomas was 18:53:29. The most commonly reported preoperative biochemical investigations were serum cortisol (average 26.4µg/dL) and ACTH (77.5pg/dL). Postoperative cortisol was most frequently used to define remission (74.8%), most commonly with threshold of 5µg/dL (44.8%). Average remission rates were 77.8% with recurrence rate of 13.9%. Median follow-up was 38 months. Majority of papers reported age (81.9%) and sex (79.4%). Only 56.6% reported whether their patients had previous pituitary surgery. 45.3% reported whether their adenomas were macroadenoma, microadenoma or undetectable. Only 24.1% reported preoperative cortisol, and this did not improve over time. 60.4% reported numerical thresholds for cortisol in defining remission, and this improved significantly over time (p = 0.004). Visual inspection of bubbleplots showed increasing preference for threshold of 5µg/dL. 70.4% reported the length of follow up. Conclusion We quantified the characteristics of Cushing’s disease, and analysed the trends in investigation and reporting. This review may help to inform future efforts in forming guidelines for research and clinical practice.

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Long-term remission of acromegaly after somatostatin analogues withdrawal: a single-centre experience

Journal of Endocrinological Investigation ◽

10.1007/s40618-021-01562-z ◽

2021 ◽

Author(s):

E. Sala ◽

G. Carosi ◽

G. Del Sindaco ◽

R. Mungari ◽

A. Cremaschi ◽

...

Keyword(s):

Median Time ◽

Pituitary Surgery ◽

Somatostatin Analogues ◽

Exclusion Criterion ◽

Single Centre ◽

Disease Evolution ◽

Single Centre Experience ◽

Pituitary Irradiation

Abstract Purpose A long-lasting remission of acromegaly after somatostatin analogues (SAs) withdrawal has been described in some series. Our aim was to update the disease evolution after SAs withdrawal in a cohort of acromegalic patients. Methods We retrospectively evaluated 21 acromegalic patients previously included in a multicentre study (Ronchi et al. 2008), updating data at the last follow-up. We added further 8 patients selected for SAs withdrawal between 2008–2018. Pituitary irradiation represented an exclusion criterion. The withdrawal was suggested after at least 9 months of clinical and hormonal disease control. Clinical and biochemical data prior and after SAs withdrawal were analysed. Results In the whole cohort (29 patients) mean age was 50 ± 14.9 years and 72.4% were females. In 69% pituitary surgery was previously performed. Overall, the median time of treatment before SAs withdrawal was 53 months (IQR = 24–84). At the last follow up in 2019, 23/29 patients (79.3%) had a disease relapse after a median time of 6 months (interquartile range or IQR = 3–12) from the drug suspension, while 6/29 (20.7%) were still on remission after 120 months (IQR = 66–150). IGF-1 levels were significantly lower before withdrawal in patients with persistent remission compared to relapsing ones (IGF-1 SDS: -1.5 ± 0.6 vs -0.11 ± 1, p = 0.01). We did not observe any other difference between patients with and without relapse, including SAs formulation, dosage and treatment duration. Conclusion A successful withdrawal of SAs is possible in a subset of well-controlled acromegalic patients and it challenges the concept that medical therapy is a lifelong requirement.

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Endoscopic transsphenoidal pituitary surgery: a good and safe primary treatment option for Cushing's disease, even in case of macroadenomas or invasive adenomas

Acta Endocrinologica ◽

10.1530/eje-13-0325 ◽

2013 ◽

Vol 169 (3) ◽

pp. 329-337 ◽

Cited By ~ 48

Author(s):

M A E M Wagenmakers ◽

H D Boogaarts ◽

S H P P Roerink ◽

H J L M Timmers ◽

N M M L Stikkelbroeck ◽

...

Keyword(s):

Treatment Option ◽

Cushing’S Disease ◽

Remission Rate ◽

Pituitary Surgery ◽

Primary Treatment ◽

Endoscopic Technique ◽

Cushing's Disease ◽

Recurrence Rates ◽

Transsphenoidal Pituitary Surgery

ContextAlthough the endoscopic technique of transsphenoidal pituitary surgery (TS) has been widely adopted, reports on its results in Cushing's disease (CD) are still scarce and no studies have investigated long-term recurrence rates. This is the largest endoscopic series published till now.ObjectiveTo gain insight into the role of endoscopic TS as a primary treatment option for CD, especially in patients with magnetic resonance imaging (MRI)-negative CD and (invasive) macroadenomas.DesignRetrospective cohort study.Patients and methodsThe medical records of 86 patients with CD who underwent endoscopic TS were examined. Data on preoperative and postoperative evaluation, perioperative complications, and follow-up were collected. Remission was defined as disappearance of clinical symptoms with a fasting plasma cortisol level ≤50 nmol/l either basal or after 1 mg dexamethasone.ResultsThe remission rate in different adenoma subclasses varied significantly: 60% in MRI-negative CD (n=20), 83% in microadenomas (n=35), 94% in noninvasive macroadenomas (n=16), and 40% in macroadenomas that invaded the cavernous sinus (n=15). The recurrence rate was 16% after 71±39 months of follow-up (mean±s.d., range 10–165 months).ConclusionsEndoscopic TS is a safe and effective treatment for all patients with CD. Recurrence rates after endoscopic TS are comparable with those reported for microscopic TS. Our data suggest that in patients with noninvasive and invasive macroadenomas, the endoscopic technique of TS should be the treatment of choice as remission rates seem to be higher than those reported for microscopic TS, although no comparative study has been performed.

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Pituitary surgery as alternative to dopamine agonists treatment for microprolactinomas, a cohort study

Acta Endocrinologica ◽

10.1530/eje-21-0293 ◽

2021 ◽

Author(s):

Bertrand Baussart ◽

Chiara Villa ◽

Anne Jouinot ◽

Marie-Laure Raffin-Sanson ◽

Luc Foubert ◽

...

Keyword(s):

Dopamine Agonists ◽

Cox Regression ◽

Disease Free Survival ◽

Pituitary Surgery ◽

Cerebrospinal Fluid Leakage ◽

Neurosurgical Department ◽

Free Survival ◽

Kaplan Meier ◽

Disease Free

Objective: Microprolactinomas are currently treated with dopamine agonists. Outcome information on microprolactinoma patients treated by surgery is limited. This study reports the first large series of consecutive non-invasive microprolactinoma patients treated by pituitary surgery and evaluates the efficiency and safety of this treatment. Design: Follow-up of a cohort of consecutive patients treated by surgery. Methods: Between January 2008 and October 2020, 114 adult patients with pure microprolactinomas were operated on in a single tertiary expert neurosurgical department, using an endoscopic endonasal transsphenoidal approach. Eligible patients were presenting a microprolactinoma with no obvious cavernous invasion on MRI. Prolactin was assayed before and after surgery. Disease-free survival was modeled using Kaplan-Meier representation. A cox regression model was used to predict remission. Results: Median follow-up was 18.2 months (range: 2.8 to 155). In this cohort, 14/114 (12%) patients were not cured by surgery, including 10 early surgical failures, and 4 late relapses occurring 37.4 months (33 to 41.8) after surgery. From Kaplan Meier estimates, 1-year and 5-year disease free survival were 90.9% (95% CI, 85.6%-96.4%) and 81% (95% CI,71.2%-92.1%) respectively. The preoperative prolactinemia was the only significant preoperative predictive factor for remission (P<0.05). No severe complication was reported, with no anterior pituitary deficiency after surgery, one diabetes insipidus, and one postoperative cerebrospinal fluid leakage properly treated by muscle plasty. Conclusions: In well selected microprolactinoma patients, pituitary surgery performed by an expert neurosurgical team is a valid first-line alternative treatment to dopamine agonists.

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Combined treatment for acromegaly with long-acting somatostatin analogs and pegvisomant: long-term safety for up to 4.5 years (median 2.2 years) of follow-up in 86 patients

Acta Endocrinologica ◽

10.1530/eje-08-0843 ◽

2009 ◽

Vol 160 (4) ◽

pp. 529-533 ◽

Cited By ~ 81

Author(s):

SJCMM Neggers ◽

WW de Herder ◽

JAMJL Janssen ◽

RA Feelders ◽

AJ van der Lely

Keyword(s):

Combined Therapy ◽

Combined Treatment ◽

Somatostatin Analogs ◽

Pituitary Surgery ◽

Median Dosage ◽

Previously Treated ◽

Long Acting

BackgroundWe previously reported on the efficacy, safety, and quality of life (QoL) of long-acting somatostatin analogs (SSA) and (twice) weekly pegvisomant (PEG-V) in acromegaly and improvement after the addition of PEG-V to long-acting SSA.ObjectiveTo assess the long-term safety in a larger group of acromegalic patients over a larger period of time: 29.2 (1.2–57.4) months (mean (range)).DesignPegvisomant was added to SSA monotherapy in 86 subjects (37 females), to normalize serum IGF1 concentrations (n=63) or to increase the QoL. The median dosage was 60.0 (20–200) mg weekly.ResultsAfter a mean treatment period of 29.2 months, 23 patients showed dose-independent PEG-V related transient liver enzyme elevations (TLEE). TLEE occurred only once during the continuation of combination therapy, but discontinuation and re-challenge induced a second episode of TLEE. Ten of these patients with TLEE also suffered from diabetes mellitus (DM). In our present series, DM had a 2.28 odds ratio (CI 1.16–9.22; p=0.03) higher risk for developing TLEE. During the combined therapy, a clinical significant decrease in tumor size by more than 20% was observed in 14 patients. Two of these patients were previously treated by pituitary surgery, 1 with additional radiotherapy and all other patients received primary medical treatment.ConclusionLong-term combined treatment with SSA and twice weekly PEG-V up to more than 4 years seems to be safe. Patients with both acromegaly and DM have a 2.28 higher risk of developing TLEE. Clinical significant tumor shrinkage was observed in 14 patients during combined treatment.

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Erectile Impotence from Veno-Occlusive Dysfunction: Our Experience and Present Diagnostic-Therapeutic Indications

Urologia Journal ◽

10.1177/039156039306000314 ◽

1993 ◽

Vol 60 (3) ◽

pp. 283-287

Author(s):

A. Meazza ◽

V. Nebulone ◽

L Musso ◽

F. Pachera ◽

G. Reali ◽

...

Keyword(s):

Dynamic Testing ◽

Diagnostic Techniques ◽

Diagnostic Methods ◽

Functional Evaluation ◽

Therapeutic Approaches ◽

Radiographic Images ◽

Non Invasive ◽

Appropriate Treatment ◽

Erectile Impotence

The authors evaluate erectile impotence from veno-occlusive dysfunction, concentrating on diagnostic techniques, both invasive and non-invasive, and appropriate treatment. In particular dynamic testing is reviewed, where a vasoactive drug, Papaverine or more recently PGE1, is injected into one of the corpora cavernosa. Measurement of blood flow velocity with Doppler ultrasonography allows a functional evaluation, while radiographic images during cavernosography give an anatomical view of the erectile abnormality. A review of case histories and partial follow-up of patients has confirmed the actual precision of the diagnostic methods and various therapeutic approaches.

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Current state of the art in the diagnosis and surgical treatment of Cushing disease: early experience with a purely endoscopic endonasal technique

Neurosurgical FOCUS ◽

10.3171/foc.2007.23.3.11 ◽

2007 ◽

Vol 23 (3) ◽

pp. 1-8 ◽

Cited By ~ 42

Author(s):

Amir R. Dehdashti ◽

Fred Gentili

Keyword(s):

Surgical Treatment ◽

Cavernous Sinus ◽

Pituitary Surgery ◽

Magnetic Resonance Images ◽

Primary Therapy ◽

Cushing Disease ◽

Endoscopic Endonasal ◽

Number Of Patients ◽

Free Cortisol

Object Transsphenoidal pituitary surgery is the primary therapy for Cushing disease because of its potential to produce lasting remission without the need for long-term drug or hormone replacement therapy. The authors evaluated the current role of pure endoscopic endonasal pituitary surgery in the treatment of Cushing disease. Methods Twenty-five patients underwent pure endoscopic surgery for confirmed Cushing disease. Thirteen patients had microadenomas and seven had macroadenomas; magnetic resonance images obtained in five patients were only suspicious or nondiagnostic, and thus they underwent inferior petrosal sinus sampling. Two patients had evidence of cavernous sinus involvement. Final histological results were consistent with adrenocorticotropin hormone (ACTH)–secreting adenoma in 20 patients. Results Twenty patients (80%) had clinical remission and laboratory confirmation of hypocortisolemia (serum cortisol < 100 nmol/L requiring substitution therapy), suppression to low-dose dexamethasone, and normal 24-hour urinary free cortisol. The median follow-up period was 17 months (range 3–32 months). There was no recurrence at the time of the last follow-up. Three patients presented with new anterior pituitary deficiency, but no one had permanent diabetes insipidus. In one patient a cerebrospinal fluid leak developed but later resolved following lumbar drainage. Treatment failure was attributable to involvement of the cavernous sinus in two patients, incomplete tumor removal in one, negative exploration in one, and nodular corticotroph hyperplasia of the pituitary gland in one. Conclusions Early results indicated that endoscopic endonasal surgery is a safe and effective treatment for ACTH-producing adenomas. The rate of remission in this study is comparable to those in previous series, and the rate of major postoperative complications is extremely low. Further studies with a larger number of patients and longer follow-ups are required to determine whether this more minimally invasive pure endoscopic approach should become the standard of care for the surgical treatment of Cushing disease.

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Outcome of using the histological pseudocapsule as a surgical capsule in Cushing disease

Journal of Neurosurgery ◽

10.3171/2008.8.jns08339 ◽

2009 ◽

Vol 111 (3) ◽

pp. 531-539 ◽

Cited By ~ 89

Author(s):

Jay Jagannathan ◽

Rene Smith ◽

Hetty L. DeVroom ◽

Alexander O. Vortmeyer ◽

Constantine A. Stratakis ◽

...

Keyword(s):

Mr Imaging ◽

Remission Rate ◽

Pituitary Surgery ◽

Anterior Lobe ◽

Accurate Identification ◽

Cushing Disease ◽

Complete Excision ◽

Imaging Results ◽

Prospective Database

Object Many patients with Cushing disease still have active or recurrent disease after pituitary surgery. The histological pseudocapsule of a pituitary adenoma is a layer of compressed normal anterior lobe that surrounds the adenoma and can be used during surgery to identify and guide removal of the tumor. In this study the authors examined the results of using the pseudocapsule as a surgical capsule in the resection of adenomas in patients with Cushing disease. Methods The authors reviewed a prospective database of data obtained in patients with Cushing disease who underwent surgery. The analysis included all cases in which a lesion was identified during surgery and in which the lesion was believed to be confined to the pituitary gland in patients with Cushing disease between January 1990 and March 2007. Since the objective was to determine the success of using the pseudocapsule as a surgical capsule, patients with invasive tumors and patients in whom no lesion was identified during surgery—challenging cases for surgical success—were excluded from analysis. Results In 261 patients an encapsulated adenoma was identified at surgery. Tumor was visible on MR imaging in 135 patients (52%); in 126 patients (48%) MR imaging detected no tumor. The range of tumor size overlapped considerably in the groups with positive and negative MR imaging results, indicating that in addition to size other features of the adenoma influence the results of MR imaging. In 252 patients hypercortisolism resolved after the first operation, whereas in 9 patients (3 with positive MR imaging and 6 with negative MR imaging) early reoperation was required. Hypercortisolism resolved in all 261 patients (256 with hypocortisolism and 5 with eucortisolism) before hospital discharge. Forty-six patients (18%) had postoperative electrolyte abnormalities (30 with hyponatremia and 16 with diabetes insipidus), but only 2 patients required treatment at discharge. The mean clinical follow-up duration was 84 months (range 12–215 months). Six patients (2%) had recurrence of hypercortisolism, all of whom were treated successfully with reoperation. Conclusions Because of their small size, adenomas can be challenging to identify in patients with Cushing disease. Use of the histological pseudocapsule of an adenoma allows accurate identification of the tumor and helps guide its complete excision. With this approach the overall remission rate is high and the rate of complications is low.

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Pituitary Apoplexy: A Retrospective Study of 33 Cases From a Single Center

Frontiers in Endocrinology ◽

10.3389/fendo.2021.656950 ◽

2021 ◽

Vol 12 ◽

Author(s):

Henrik Falhammar ◽

Sofia Tornvall ◽

Charlotte Höybye

Keyword(s):

Pituitary Apoplexy ◽

Pituitary Surgery ◽

University Hospital ◽

Single Center ◽

Precipitating Factors ◽

Threatening Condition ◽

Life Threatening ◽

Inhomogeneous Condition ◽

Neurosurgical Intervention

PurposeAcute symptomatic pituitary apoplexy is a rare and potentially life-threatening condition. However, pituitary apoplexy can also present with milder symptoms and stable hemodynamics. Due to the rarity of this inhomogeneous condition, clinical studies are important to increase the knowledge.MethodsWe retrospectively reviewed all consecutive cases of pituitary apoplexy being admitted between January 1st, 2005 and December 31st, 2019 at the Karolinska University Hospital, Stockholm, Sweden, for symptoms, results of magnetic resonance (MRI), biochemistry, management and mortality.ResultsThirty-three patients were identified with pituitary apoplexy, 18 were men (55%) and mean age was 46.5 (17.2) years. The incidence of symptomatic pituitary apoplexy was 1.6 patients/year (0.76 patients/1,000,000 inhabitants/year). The majority presented with headache (n=27, 82%) and hormonal deficiencies (n=18, 55%), which were most frequent in men. ACTH deficiency was present in nine patients (27% but 50% of those with hormonal deficiencies). All had the characteristic findings on MRI. Only three patients (9%) required acute pituitary surgery, while eight were operated after more than one week. Seven (21%) were on antithrombotic therapy. None of the patients died in the acute course. During follow-up (7.6 ± 4.3 years) none of the hormonal deficiencies regressed and 3 patients died from non-related causes.ConclusionOur study confirmed the rarity and the symptoms of this condition. Surprisingly, only 3 patients needed acute neurosurgical intervention, perhaps due to milder cases and a general intensified treatment of precipitating factors. An early awareness and in severe cases decision on pituitary surgery is of utmost importance to avoid severe complications.

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